{"id":891,"date":"2020-08-25T22:29:23","date_gmt":"2020-08-25T22:29:23","guid":{"rendered":"https:\/\/lorandparajdi.wordpress.com\/?page_id=891"},"modified":"2023-11-24T18:58:23","modified_gmt":"2023-11-24T18:58:23","slug":"assessing-measurable-residual-disease-in-chronic-myeloid-leukemia-bcr-abl1-is-in-the-avant-garde-of-molecular-hematology","status":"publish","type":"page","link":"https:\/\/www.cs.ubbcluj.ro\/~lorand\/assessing-measurable-residual-disease-in-chronic-myeloid-leukemia-bcr-abl1-is-in-the-avant-garde-of-molecular-hematology\/","title":{"rendered":"Article no.3"},"content":{"rendered":"\n

Assessing Measurable Residual Disease in Chronic Myeloid Leukemia. BCR-ABL1 IS in the Avant-Garde<\/em> of Molecular HematologyResearch Paper, September 23, 2019 \/ Lorand Gabriel Parajdi<\/span><\/a><\/p>\n\n\n\n

Published in Frontiers in Oncology, Hematologic Malignancies<\/em> 9, 863,<\/em> DOI: <\/a>10.3389\/fonc.2019.00863<\/span><\/a>, 2019<\/em>.<\/p>\n\n\n\n

\"\"  The full paper is available on Frontiers in Oncology, Hematologic Malignancies website:<\/span><\/strong><\/a>https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2019.00863\/full<\/span><\/a><\/a>and the supplementary material is available at<\/span><\/strong> <\/a>https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2019.00863\/full#supplementary-material<\/span><\/a><\/p>\n\n\n\n

Authors:<\/mark><\/strong> Vlad Moisoiu1<\/sup>, Patric Teodorescu1,2<\/sup>, Lorand Parajdi3<\/sup>, Sergiu Pasca1<\/sup>, Mihnea Zdrenghea1<\/sup>, Delia Dima2<\/sup>, Radu Precup3<\/sup>, Ciprian Tomuleasa2,4<\/sup> and Simona Soverini5<\/sup> <\/p>\n\n\n\n

<\/a>1<\/sup> Department of Hematology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania <\/a>2<\/sup> Department of Hematology, “Ion Chiricu\u021b\u0103” Clinical Research Center, Cluj-Napoca, Romania <\/a>3<\/sup> Department of Mathematics, “Babe\u0219-Bolyai” University, Cluj-Napoca, Romania <\/a>4<\/sup> Department of Hematology, Research Center for Functional Genomics and Translational Medicine, “Iuliu Ha\u021bieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania <\/a>5<\/sup> Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology L. and A. Ser\u00e0gnoli, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy <\/p>\n\n\n\n

Abstract:<\/span><\/strong> Chronic myelogenous leukemia (CML) is a malignancy of the myeloid cell lineage characterized by a recurrent chromosomal abnormality: the Philadelphia chromosome, which results from the reciprocal translocation of the chromosomes 9 and 22. The Philadelphia chromosome contains a fusion gene called BCR-ABL1. The BCR-ABL1 codes for an aberrantly functioning tyrosine kinase that drives the malignant proliferation of the founding clone. The advent of tyrosine kinase inhibitors (TKI) represents a landmark in the treatment of CML, that has led to tremendous improvement in the remission and survival rates. Since the introduction of imatinib, the first TKI, several other TKI have been approved that further broadened the arsenal against CML. Patients treated with TKIs require sensitive monitoring of BCR-ABL1 transcripts with quantitative real-time polymerase chain reaction (qRT-PCT), which has become an essential part of managing patients with CML. In this review, we discuss the importance of the BCR-ABL1 assay, and we highlight the growing importance of BCR-ABL1 dynamics. We also introduce a mathematical correction for the BCR-ABL1 assay that could help homogenizing the use of the ABL1 as a control gene. Finally, we discuss the growing body of evidence concerning treatment-free remission. Along with the continuous improvement in the therapeutic arsenal against CML, the molecular monitoring of CML represents the avant-garde<\/em> in the struggle to make CML a curable disease.<\/p>\n\n\n\n

Keywords<\/strong>:<\/mark> Chronic myeloid leukemia; Mathematical modeling; BCR-ABL; IS; Treatment free remission.<\/p>\n\n\n\n

Cite As:<\/mark><\/strong>  Moisoiu V, Teodorescu P, Parajdi L, Pasca S, Zdrenghea M, Dima D, Precup R, Tomuleasa C and Soverini S (2019) Assessing measurable residual disease in chronic myeloid leukemia. BCR-ABL1 IS in the avant-garde<\/em> of molecular hematology. Front. Oncol.<\/em> 9:863. DOI: 10.3389\/fonc.2019.00863<\/p>\n\n\n\n

This article was awarded by UEFISCDI.gov<\/a> in the competition “The Awards of the Research Results Published in 2019” (PRECISI 2019). For the results see: https:\/\/uefiscdi.gov.ro\/resource-823937-precisi_2019_lista-17<\/a><\/strong><\/p>\n\n\n\n

References:<\/strong> <\/mark>
1.<\/mark><\/strong> Jabbour E, Kantarjian H. Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring.<\/em>\u00a0Am J Hematol. (2016<\/strong>) 91:252\u201365. [Article]<\/mark><\/a>

2.<\/mark><\/strong> Quint\u00e1s-Cardama A, Cortes J. Molecular biology of bcr-abl1\u2013positive chronic myeloid leukemia.<\/em>\u00a0Blood. (2009<\/strong>) 113:1619\u201330. [Article]<\/mark><\/a>

3<\/mark>.<\/strong> Koretzky GA. The legacy of the Philadelphia chromosome.<\/em>\u00a0J Clin Invest. (2007<\/strong>) 117:2030\u20132. [Article]<\/mark><\/a>\u00a0

4<\/mark>.<\/strong> Hochhaus A, Saussele S, Rosti G, Mahon FX, Janssen JJWM, Hjorth-Hansen H, et al. Chronic myeloid leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.<\/em>\u00a0Ann Oncol. (2017<\/strong>) 28 (Suppl. 4):iv41\u2013iv51. [Article]<\/mark><\/a>\u00a0

5<\/mark>.<\/strong> Chase A, Huntly BJP, Cross NCP. Cytogenetics of chronic myeloid leukaemia.<\/em>\u00a0Best Pract Res Clin Haematol. (2001<\/strong>) 14:553\u201371. [Article]<\/mark><\/a>

6<\/mark>.<\/strong> Morris CM. Chronic myeloid leukemia: cytogenetic methods and applications for diagnosis and treatment.<\/em>\u00a0Methods Mol Biol.\u00a0(2011<\/strong>) 730:33\u201361. [Article]<\/mark><\/a>

7<\/mark>.<\/strong> Wang W, Cortes JE, Tang G, Khoury JD, Wang S, Bueso-Ramos CE, et al. Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy.<\/em>\u00a0Blood. (2016<\/strong>) 127:2742\u201350. [Article]<\/mark><\/a>

8<\/mark>.<\/strong> Chen Z, Shao C, Wang W, Zuo Z, Mou X, Hu SJ, et al. Cytogenetic landscape and impact in blast phase of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy.<\/em>\u00a0Leukemia. (2017<\/strong>) 31:585\u201392. [Article]<\/mark><\/a>\u00a0

9<\/mark>.<\/strong> Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia.<\/em>\u00a0N Engl J Med. (2017<\/strong>) 376:917\u201327. [Article]<\/mark><\/a>

10<\/mark>.<\/strong> O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.<\/em>\u00a0N Engl J Med. (2003<\/strong>) 348:994\u20131004. [Article]<\/mark><\/a>

11<\/mark>.<\/strong> Hochhaus A, Druker BJ, Larson RA, O’Brien SG, Gathmann I, Guilhot F. IRIS 6-year follow-up: sustained survival and declining annual rate of transformation in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib.<\/em>\u00a0Blood. (2007<\/strong>) 110:25. [Google Scholar]<\/mark><\/a>

12<\/mark>.<\/strong> Luu MH, Press RD. BCR-ABL PCR testing in chronic myelogenous leukemia: molecular diagnosis for targeted cancer therapy and monitoring.<\/em>\u00a0Expert Rev Mol Diagnos. (2013<\/mark><\/strong>) 13:749\u201362. [Article]<\/mark><\/a>

13.<\/mark><\/strong> Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boqu\u00e9 C, et al. Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-na\u00efve chronic myeloid leukemia patients trial.<\/em>\u00a0J Clin Oncol. (2016) 34:2333\u201340. [Article]<\/mark><\/a>

14<\/mark>.<\/strong> Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim DW, Issaragrisil S, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial.<\/em>\u00a0Leukemia. (2016<\/strong>) 30:1044\u201354. [Article]<\/mark><\/a>

15<\/mark>.<\/strong> Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial.<\/em>\u00a0J Clin Oncol.\u00a0(2018<\/strong>) 36:231\u20137. [Article]<\/mark><\/a>

16<\/mark>.<\/strong> Lipton JH, Chuah C, Guerci-Bresler A, Rosti G, Simpson D, Assouline S, et al. Epic: a phase 3 trial of ponatinib compared with imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CP-CML).<\/em>\u00a0Blood. (2014<\/strong>) 124:519. [Article]<\/mark><\/a>

17<\/mark>.<\/strong> Mahon F-X, Etienne G. Deep molecular response in chronic myeloid leukemia: the new goal of therapy?<\/em>\u00a0Clin Cancer Res.\u00a0(2014<\/strong>) 20:310\u201322. [Article]<\/mark><\/a>

18.<\/mark><\/strong> Keating GM. Dasatinib: a review in chronic myeloid leukaemia and Ph+ acute lymphoblastic leukaemia.<\/em>\u00a0Drugs.\u00a0(2017<\/strong>) 77:85\u201396. [Article]<\/mark><\/a>

19.<\/mark><\/strong> Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassmann B, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive <\/em>ALL.\u00a0N Engl J Med. (2006<\/strong>) 354:2542\u201351. [Article]<\/mark><\/a>

20.<\/mark><\/strong> Cortes JE, Kim DW, Kantarjian HM, Brummendorf TH, Dyagil I, Griskevicius L, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial.<\/em>\u00a0J Clin Oncol. (2012<\/strong>) 30:3486\u201392. [Article]<\/mark><\/a>

21.<\/mark><\/strong> O’Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, et al. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance.<\/em>\u00a0Cancer Cell. (2009<\/strong>) 16:401\u201312. [Article]<\/mark><\/a>

22.<\/mark><\/strong> Verma D, Kantarjian HM, Jones D, Luthra R, Borthakur G, Verstovsek S, et al. Chronic myeloid leukemia (CML) with P190 BCR-ABL: analysis of characteristics, outcomes, and prognostic significance.<\/em>\u00a0Blood. (2009<\/strong>) 114:2232\u20135. [Article]<\/mark><\/a>

23.<\/mark><\/strong> Zabriskie MS, Eide CA, Tantravahi SK, Vellore NA, Estrada J, Nicolini FE, et al. BCR-ABL1 compound mutations combining key kinase domain positions confer clinical resistance to ponatinib in Ph chromosome-positive leukemia.<\/em>\u00a0Cancer Cell. (2014<\/strong>) 26:428\u201342. [Article]<\/mark><\/a>

24<\/mark>.<\/strong> Kantarjian HM, Cortes JE, Kim DW, Khoury HJ, Brummendorf TH, Porkka K, et al. Bosutinib safety and management of toxicity in leukemia patients with resistance or intolerance to imatinib and other tyrosine kinase inhibitors.<\/em>\u00a0Blood. (2014<\/strong>) 123:1309\u201318. [Google Scholar]<\/mark><\/a>

25.<\/strong><\/mark> Rossari F, Minutolo F, Orciuolo E. Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy.<\/em>\u00a0J Hematol Oncol. (2018<\/strong>) 11:84. [Article]<\/mark><\/a>

26<\/mark>.<\/strong> Thomas J, Wang L, Clark RE, Pirmohamed M. Active transport of imatinib into and out of cells: implications for drug resistance.<\/em>\u00a0Blood. (2004<\/strong>) 104:3739\u201345. [Article]<\/mark><\/a>

27<\/mark>.<\/strong> Hegedus C, Ozvegy-Laczka C, Apati A, Magocsi M, Nemet K, Orfi L, et al. Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties.<\/em>\u00a0Br J Pharmacol. (2009<\/strong>) 158:1153\u201364. [Article]<\/mark><\/a>

28<\/mark>.<\/strong> Picard S, Titier K, Etienne G, Teilhet E, Ducint D, Bernard MA, et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia.<\/em>\u00a0Blood.\u00a0(2007<\/strong>) 109:3496\u20139. [Article]<\/mark><\/a>

29<\/mark>.<\/strong> Larson RA, Druker BJ, Guilhot F, O’Brien SG, Riviere GJ, Krahnke T, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study.<\/em>\u00a0Blood. (2008<\/strong>) 111:4022\u20138. [Article]<\/mark><\/a>

30.<\/mark><\/strong> Bouchet S, Titier K, Moore N, Lassalle R, Ambrosino B, Poulette S, et al. Therapeutic drug monitoring of imatinib in chronic myeloid leukemia: experience from 1216 patients at a centralized laboratory.<\/em>\u00a0Fundam Clin Pharmacol.\u00a0(2013<\/strong>) 27:690\u20137. \u00a0[Article]<\/mark><\/a>

31<\/mark>.<\/strong> Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J, et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis.<\/em>\u00a0Blood. (2003<\/strong>) 102:276\u201383. [Article]<\/mark><\/a>

32.<\/mark><\/strong> Soverini S, Martinelli G, Rosti G, Bassi S, Amabile M, Poerio A, et al. ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia.<\/em>\u00a0J Clin Oncol.\u00a0(2005<\/strong>) 23:4100\u20139. [Article]<\/mark><\/a>

33.<\/mark><\/strong> Nicolini FE, Corm S, Le QH, Sorel N, Hayette S, Bories D, et al. Mutation status and clinical outcome of 89 imatinib mesylate-resistant chronic myelogenous leukemia patients: a retrospective analysis from the French intergroup of CML (Fi(phi)-LMC GROUP).<\/em>\u00a0Leukemia. (2006<\/strong>) 20:1061\u20136. [Article]<\/mark><\/a>

34.<\/mark><\/strong> Soverini S, Colarossi S, Gnani A, Rosti G, Castagnetti F, Poerio A, et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: by the GIMEMA Working Party on Chronic Myeloid Leukemia.<\/em>\u00a0Clin Cancer Res.\u00a0(2006<\/strong>) 12:7374\u20139. [Article]<\/mark><\/a>

35.<\/mark><\/strong> Khorashad JS, de Lavallade H, Apperley JF, Milojkovic D, Reid AG, Bua M, et al. Finding of kinase domain mutations in patients with chronic phase chronic myeloid leukemia responding to imatinib may identify those at high risk of disease progression.<\/em>\u00a0J Clin Oncol.\u00a0(2008<\/strong>) 26:4806\u201313. [Article]<\/mark><\/a>

36.<\/mark><\/strong> Soverini S, Gnani A, Colarossi S, Castagnetti F, Abruzzese E, Paolini S, et al. Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors.<\/em>\u00a0Blood<\/em>. (2009<\/strong>) 114:2168\u201371. [Article]<\/mark><\/a>

37.<\/mark><\/strong> Itonaga H, Tsushima H, Hata T, Matsuo E, Imanishi D, Imaizumi Y, et al. Successful treatment of a chronic-phase T-315I-mutated chronic myelogenous leukemia patient with a combination of imatinib and interferon-alfa.<\/em>\u00a0Int J Hematol. (2012<\/strong>) 95:209\u201313. [Article]<\/mark><\/a>

38.<\/mark><\/strong> Tomuleasa C, Dima D, Frinc I, Patiu M, Petrushev B, Cucuianu A, et al. BCR-ABL1 T315I mutation, a negative prognostic factor for the terminal phase of chronic myelogenous leukemia treated with first- and second-line tyrosine kinase inhibitors, might be an indicator of allogeneic stem cell transplant as the treatment of choice.<\/em>\u00a0Leuk Lymphoma. (2015<\/strong>) 56:546\u20137. [Article]<\/mark><\/a>

39.<\/mark><\/strong> Yun S, Vincelette ND, Segar JM, Dong Y, Shen Y, Kim DW, et al. Comparative effectiveness of newer tyrosine kinase inhibitors versus imatinib in the first-line treatment of chronic-phase chronic myeloid leukemia across risk groups: a systematic review and meta-analysis of eight randomized trials.<\/em>\u00a0Clin Lymphoma Myeloma Leuk.\u00a0(2016<\/strong>) 16:e85\u201394. [Article]<\/mark><\/a>

40.<\/mark><\/strong> Hughes TP, Saglio G, Quintas-Cardama A, Mauro MJ, Kim DW, Lipton JH, et al. BCR-ABL1 mutation development during first-line treatment with dasatinib or imatinib for chronic myeloid leukemia in chronic phase.<\/em>\u00a0Leukemia. (2015<\/strong>) 29:1832\u20138. [Article]<\/mark><\/a>

41.<\/mark><\/strong> Jabbour E, Kantarjian H, Jones D, Breeden M, Garcia-Manero G, O’Brien S, et al. Characteristics and outcomes of patients with chronic myeloid leukemia and T315I mutation following failure of imatinib mesylate therapy.<\/em>\u00a0Blood.\u00a0(2008<\/strong>) 112:53\u20135. [Article]<\/mark><\/a>

42.<\/mark><\/strong> Jabbour E, Kantarjian HM, Jones D, Reddy N, O’Brien S, Garcia-Manero G, et al. Characteristics and outcome of chronic myeloid leukemia patients with F317L BCR-ABL kinase domain mutation after therapy with tyrosine kinase inhibitors.<\/em>\u00a0Blood. (2008<\/strong>) 112:4839\u201342. [Article]<\/mark><\/a>

43.<\/mark><\/strong> Muller MC, Cortes JE, Kim DW, Druker BJ, Erben P, Pasquini R, et al. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations<\/em>.\u00a0Blood.\u00a0(2009<\/strong>) 114:4944\u201353. [Article]<\/mark><\/a>

44.<\/mark><\/strong> Hughes T, Saglio G, Branford S, Soverini S, Kim DW, Muller MC, et al. Impact of baseline BCR-ABL mutations on response to nilotinib in patients with chronic myeloid leukemia in chronic phase.<\/em>\u00a0J Clin Oncol.\u00a0(2009<\/strong>) 27:4204\u201310. [Article]<\/mark><\/a>

45.<\/mark><\/strong> Okabe S, Tauchi T, Tanaka Y, Katagiri S, Kitahara T, Ohyashiki K. Activity of omacetaxine mepesuccinate against ponatinib-resistant BCR-ABL-positive cells.<\/em>\u00a0Blood.\u00a0(2013<\/strong>) 122:3086\u20138. [Article]<\/mark><\/a>

46.<\/mark><\/strong> Li YF, Deng ZK, Xuan HB, Zhu JB, Ding BH, Liu XN, et al. Prolonged chronic phase in chronic myelogenous leukemia after homoharringtonine therapy.<\/em>\u00a0Chin Med J. (2009<\/strong>) 122:1413\u20137. [Article]<\/mark><\/a>

47.<\/mark><\/strong> Quintas-Cardama A, Kantarjian H, Cortes J. Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009.<\/em>\u00a0Cancer. (2009<\/strong>) 115:5382\u201393. [Article]<\/mark><\/a>

48.<\/mark><\/strong> Deininger MW, Hodgson JG, Shah NP, Cortes JE, Kim DW, Nicolini FE, et al. Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients.<\/em>\u00a0Blood. (2016<\/strong>) 127:703\u201312. [Article]<\/mark><\/a>

49.<\/mark><\/strong> Saglio G, Fava C. BCR-ABL1 mutation not equal ponatinib resistance.<\/em>\u00a0Blood.\u00a0(2016<\/strong>) 127:666\u20137. [Article]<\/mark><\/a>

50.<\/mark><\/strong> Chhabra S, Ahn KW, Hu ZH, Jain S, Assal A, Cerny J, et al. Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia.<\/em>\u00a0Blood Adv. (2018<\/strong>) 2:2922\u201336. [Article]<\/mark><\/a>

51.<\/mark><\/strong> Jain P, Kantarjian HM, Ghorab A, Sasaki K, Jabbour EJ, Nogueras Gonzalez G, et al. Prognostic factors and survival outcomes in patients with chronic myeloid leukemia in blast phase in the tyrosine kinase inhibitor era: cohort study of 477 patients.<\/em>\u00a0Cancer. (2017<\/strong>) 123:4391\u2013402. [Article]<\/mark><\/a>

52.<\/mark><\/strong> Saussele S, Silver RT. Management of chronic myeloid leukemia in blast crisis.<\/em>\u00a0Ann Hematol. (2015<\/strong>) 94 (Suppl. 2):S159\u201365. [Article]<\/mark><\/a>

53.<\/mark><\/strong> Hehlmann R. How I treat CML blast crisis.<\/em>\u00a0Blood.\u00a0(2012<\/strong>) 120:737\u201347. [Article]<\/mark><\/a>

54.<\/mark><\/strong> Rosshandler Y, Shen AQ, Cortes J, Khoury HJ. Omacetaxine mepesuccinate for chronic myeloid leukemia.\u00a0<\/em>Expert Rev Hematol. (2016<\/strong>) 9:419\u201324. [Article]<\/mark><\/a>

55.<\/mark><\/strong> Nicolini FE, Khoury HJ, Akard L, Rea D, Kantarjian H, Baccarani M, et al. Omacetaxine mepesuccinate for patients with accelerated phase chronic myeloid leukemia with resistance or intolerance to two or more tyrosine kinase inhibitors.<\/em>\u00a0Haematologica. (2013<\/strong>) 98:e78\u20139. [Article]<\/mark><\/a>

56.<\/mark><\/strong> Soverini S, Rosti G, Baccarani M, Martinelli G. Molecular monitoring.<\/em>\u00a0Curr Hematol Malig Rep. (2014<\/strong>) 9:1\u20138. [Article]<\/mark><\/a>

57.<\/mark><\/strong> Menif S, Zarrouki S, Jeddi R, ben Alaya N, Ali ZB, Ben Abid H, et al. Quantitative detection of bcr-abl transcripts in chronic myeloid leukemia.<\/em>\u00a0Pathol Biol. (2009<\/strong>) 57:388\u201391. [Article]<\/mark><\/a>

58.<\/mark><\/strong> Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia.<\/em>\u00a0N Engl J Med. (2003<\/strong>) 349:1423\u201332. [Article]<\/mark><\/a>

59.<\/mark><\/strong> Press RD, Kamel-Reid S, Ang D. BCR-ABL1 RT-qPCR for monitoring the molecular response to tyrosine kinase inhibitors in chronic myeloid leukemia.<\/em>\u00a0J Mol Diagnos. (2013<\/strong>) 15:565\u201376. [Article]<\/mark><\/a>

60.<\/mark><\/strong> Branford S, Fletcher L, Cross NC, Muller MC, Hochhaus A, Kim DW, et al. Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials.<\/em>\u00a0Blood. (2008<\/strong>) 112:3330\u20138. [Article]<\/mark><\/a>

61.<\/mark><\/strong> Beillard E, Pallisgaard N, van der Velden VH, Bi W, Dee R, van der Schoot E, et al. Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using \u2018real-time\u2019 quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR) – a Europe against cancer program.<\/em>\u00a0Leukemia. (2003<\/strong>) 17:2474\u201386. [Article]<\/mark><\/a>

62.<\/mark><\/strong> Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia.<\/em>\u00a0N Engl J Med. (2006<\/strong>) 355:2408\u201317. [Article]<\/mark><\/a>

63.<\/mark><\/strong> Press RD, Galderisi C, Yang R, Rempfer C, Willis SG, Mauro MJ, et al. A half-log increase in BCR-ABL RNA predicts a higher risk of relapse in patients with chronic myeloid leukemia with an imatinib-induced complete cytogenetic response.<\/em>\u00a0Clin Cancer Res.\u00a0(2007<\/strong>) 13:6136\u201343. [Article]<\/mark><\/a>

64.<\/mark><\/strong> de Lavallade H, Apperley JF, Khorashad JS, Milojkovic D, Reid AG, Bua M, et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis.<\/em>\u00a0J Clin Oncol. (2008<\/strong>) 26:3358\u201363. [Article]<\/mark><\/a>

65.<\/mark><\/strong> Marin D, Milojkovic D, Olavarria E, Khorashad JS, de Lavallade H, Reid AG, et al. European leukemianet criteria for failure or suboptimal response reliably identify patients with CML in early chronic phase treated with imatinib whose eventual outcome is poor.<\/em>\u00a0Blood.\u00a0(2008<\/strong>) 112:4437\u201344. [Article]<\/mark><\/a>

66.<\/mark><\/strong> Hehlmann R, Lauseker M, Jung-Munkwitz S, Leitner A, Muller MC, Pletsch N, et al. Tolerability-adapted imatinib 800 mg\/d versus 400 mg\/d versus 400 mg\/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia.<\/em>\u00a0J Clin Oncol. (2011<\/strong>) 29:1634\u201342. [Article]<\/mark><\/a>

67.<\/mark><\/strong> Saussele S, Hehlmann R, Fabarius A, Jeromin S, Proetel U, Rinaldetti S, et al. Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV.<\/em>\u00a0Leukemia. (2018<\/strong>) 32:1222\u20138. [Article]<\/mark><\/a>

68.<\/mark><\/strong> Hehlmann R, Lauseker M, Hanfstein B, M\u00fcller MC, Schreiber A, Proetel U, et al. Complete molecular remission (CMR 4.5) of CML is induced faster by dose \u2013 optimized imatinib and predicts better survival – results from the randomized CML-study IV.<\/em>\u00a0Blood. (2012<\/strong>) 120:67. [Google Scholar]<\/mark><\/a>

69.<\/mark><\/strong> Falchi L, Kantarjian HM, Quintas-Cardama A, Brien S, Jabbour EJ, Ravandi F, et al. Clinical significance of deeper molecular responses with four modalities of tyrosine kinase inhibitors as frontline therapy for chronic myeloid leukemia.<\/em>\u00a0Blood.\u00a0(2012<\/strong>) 120:164. [Google Scholar]<\/mark><\/a>

70.<\/mark><\/strong> Etienne G, Nicolini NE, Dulucq S, Schmitt A, Hayette S, Lippert \u00c9, et al. Achieving a complete molecular remission under imatinib therapy is associated with a better outcome in chronic phase chronic myeloid leukaemia patients on imatinib frontline therapy.<\/em>\u00a0Blood.\u00a0(2012<\/strong>) 120:3754. [Article]<\/mark><\/a>

71.<\/mark><\/strong> Hehlmann R, Lauseker M, Saussele S, Pfirrmann M, Krause S, Kolb HJ, et al. Assessment of imatinib as first-line treatment of chronic myeloid leukemia: 10-year survival results of the randomized CML study IV and impact of non-CML determinants.<\/em>\u00a0Leukemia.\u00a0(2017<\/strong>) 31:2398\u2013406. [Article]<\/mark><\/a>

72.<\/mark><\/strong> Hanfstein B, Muller MC, Hehlmann R, Erben P, Lauseker M, Fabarius A, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML).<\/em>\u00a0Leukemia. (2012<\/strong>) 26:2096\u2013102. [Article]<\/mark><\/a>

73.<\/mark><\/strong> Marin D, Ibrahim AR, Lucas C, Gerrard G, Wang L, Szydlo RM, et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.<\/em>\u00a0J Clin Oncol.\u00a0(2012<\/strong>) 30:232\u20138. [Article]<\/mark><\/a>

74.<\/mark><\/strong> Huet S, Cony-Makhoul P, Heiblig M, Tigaud I, Gazzo S, Belhabri A, et al. Major molecular response achievement in CML Patients can be predicted by BCR-ABL1\/ABL1 or BCR-ABL1\/GUS ratio at an earlier time point of follow-up than currently recommended.<\/em>\u00a0PLoS ONE. (2014<\/strong>) 9:e106250-e. [Article]<\/mark><\/a>

75.<\/mark><\/strong> Iriyama N, Fujisawa S, Yoshida C, Wakita H, Chiba S, Okamoto S, et al. Shorter halving time of BCR-ABL1 transcripts is a novel predictor for achievement of molecular responses in newly diagnosed chronic-phase chronic myeloid leukemia treated with dasatinib: results of the D-first study of Kanto CML study group.<\/em>\u00a0Am J Hematol. (2015<\/strong>) 90:282\u20137. [Article]<\/mark><\/a>

76.<\/mark><\/strong> Fava C, Rege-Cambrin G, Dogliotti I, Gottardi E, Berchialla P, Di Gioacchino B, et al. Early BCR-ABL1 reduction is predictive of better event-free survival in patients with newly diagnosed chronic myeloid leukemia treated with any tyrosine kinase inhibitor.<\/em>\u00a0Clin Lymphoma Myeloma Leuk.\u00a0(2016<\/strong>) 16 (Suppl.):S96\u2013100. [Article]<\/mark><\/a>

77.<\/mark><\/strong> Branford S, Yeung DT, Parker WT, Roberts ND, Purins L, Braley JA, et al. Prognosis for patients with CML and >10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline.<\/em>\u00a0Blood.\u00a0(2014<\/strong>) 124:511\u20138. [Article]<\/mark><\/a>

78.<\/mark><\/strong> Hanfstein B, Shlyakhto V, Lauseker M, Hehlmann R, Saussele S, Dietz C, et al. Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib.<\/em>\u00a0Leukemia.\u00a0(2014<\/strong>) 28:1988\u201392. [Article]<\/mark><\/a>

79.<\/mark><\/strong> Gale RP, Hochhaus A. Therapy-free remission in chronic myeloid leukemia: possible mechanism.<\/em>\u00a0Expert Rev Hematol. (2018<\/strong>) 11:269\u201372. [Article]<\/mark><\/a>

80.<\/mark><\/strong> Rousselot P, Huguet F, Rea D, Legros L, Cayuela JM, Maarek O, et al. Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years.<\/em>\u00a0Blood. (2007<\/strong>) 109:58\u201360. [Article]<\/mark><\/a>

81.<\/mark><\/strong> Mahon FX, Delbrel X, Cony-Makhoul P, Faberes C, Boiron JM, Barthe C, et al. Follow-up of complete cytogenetic remission in patients with chronic myeloid leukemia after cessation of interferon alfa.<\/em>\u00a0J Clin Oncol.\u00a0(2002<\/strong>) 20:214\u201320. [Article]<\/mark><\/a>

82.<\/mark><\/strong> Cortes J, O’Brien S, Kantarjian H. Discontinuation of imatinib therapy after achieving a molecular response.<\/em>\u00a0Blood.\u00a0(2004<\/strong>) 104:2204\u20135. [Article]<\/mark><\/a>\u00a0

83.<\/mark><\/strong> Sau\u00dfele S, Richter J, Hochhaus A, Mahon FX. The concept of treatment-free remission in chronic myeloid leukemia.<\/em>\u00a0Leukemia.\u00a0(2016<\/strong>) 30:1638\u201347. [Article]<\/mark><\/a>

84.<\/mark><\/strong> Corbin AS, Agarwal A, Loriaux M, Cortes J, Deininger MW, Druker BJ. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity.<\/em>\u00a0J Clin Invest. (2011<\/strong>) 121:396\u2013409. [Article]<\/mark><\/a>

85.<\/mark><\/strong> Hamilton A, Helgason GV, Schemionek M, Zhang B, Myssina S, Allan EK, et al. Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival.<\/em>\u00a0Blood.\u00a0(2012<\/strong>) 119:1501\u201310. [Article]<\/mark><\/a>

86.<\/mark><\/strong> Ilander M, Olsson-Stromberg U, Schlums H, Guilhot J, Bruck O, Lahteenmaki H, et al. Increased proportion of mature NK cells is associated with successful imatinib discontinuation in chronic myeloid leukemia.<\/em>\u00a0Leukemia. (2017<\/strong>) 31:1108\u201316. [Article]<\/mark><\/a>

87.<\/mark><\/strong> Hughes A, Clarson J, Tang C, Vidovic L, White DL, Hughes TP, et al. CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors.<\/em>\u00a0Blood.\u00a0(2017<\/strong>) 129:1166\u201376. [Article]<\/mark><\/a>

88.<\/mark><\/strong> Gale RP, Opelz G. Is there immune surveillance against chronic myeloid leukaemia? Possibly, but not much.<\/em>\u00a0Leuk Res. (2017<\/strong>) 57:109\u201311. [Article]<\/mark><\/a>

89.<\/mark><\/strong> Hsu WL, Preston DL, Soda M, Sugiyama H, Funamoto S, Kodama K, et al. The incidence of leukemia, lymphoma and multiple myeloma among atomic bomb survivors: 1950\u20132001.<\/em>\u00a0Radi Res. (2013<\/strong>) 179:361\u201382. [Article]<\/mark><\/a> <\/mark>

90.<\/mark><\/strong> Roeder I, Horn M, Glauche I, Hochhaus A, Mueller MC, Loeffler M. Dynamic modeling of imatinib-treated chronic myeloid leukemia: functional insights and clinical implications.<\/em>\u00a0Nat Med. (2006<\/strong>) 12:1181\u20134. [Article]<\/mark><\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Assessing Measurable Residual Disease in Chronic Myeloid Leukemia. BCR-ABL1 IS in the Avant-Garde of Molecular HematologyResearch Paper, September 23, 2019 \/ Lorand Gabriel Parajdi Published in Frontiers in Oncology, Hematologic Malignancies 9, 863, DOI: 10.3389\/fonc.2019.00863, 2019.   The full paper is available on Frontiers in Oncology, Hematologic Malignancies website:https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2019.00863\/fulland the supplementary material is available at https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2019.00863\/full#supplementary-material Authors: Vlad … Continue reading Article no.3<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/www.cs.ubbcluj.ro\/~lorand\/wp-json\/wp\/v2\/pages\/891"}],"collection":[{"href":"https:\/\/www.cs.ubbcluj.ro\/~lorand\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.cs.ubbcluj.ro\/~lorand\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.cs.ubbcluj.ro\/~lorand\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.cs.ubbcluj.ro\/~lorand\/wp-json\/wp\/v2\/comments?post=891"}],"version-history":[{"count":28,"href":"https:\/\/www.cs.ubbcluj.ro\/~lorand\/wp-json\/wp\/v2\/pages\/891\/revisions"}],"predecessor-version":[{"id":5554,"href":"https:\/\/www.cs.ubbcluj.ro\/~lorand\/wp-json\/wp\/v2\/pages\/891\/revisions\/5554"}],"wp:attachment":[{"href":"https:\/\/www.cs.ubbcluj.ro\/~lorand\/wp-json\/wp\/v2\/media?parent=891"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}