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03.02.2023 | Original Article

Molecular genetics and management of world health organization defined atypical chronic myeloid leukemia

verfasst von: Yingxin Sun, Qinrong Wang, Xingxia Zhang, Zhiyu Zhang, Qian Wang, Jiannong Cen, Mingqing Zhu, Jinlan Pan, Dandan Liu, Depei Wu, Yifeng Cai, Suning Chen

Erschienen in: Annals of Hematology | Ausgabe 4/2023

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Abstract

Atypical chronic myeloid leukemia (CML) is a rare BCR::ABL1-negative hematopoietic stem cell disease characterized by granulocytic proliferation and granulocytic dysplasia. Due to both the challenging diagnosis and the rarity of atypical CML, comprehensive molecular annotation-based analyses of this disease population have been scarce, and it is currently difficult to identify the optimal treatment for atypical CML. To explore atypical CML genomic landscape and treatment options, we performed a systematic retrospective of the clinical data and outcomes of 31 atypical CML patients. We observed that the molecular landscape of atypical CML was highly heterogeneous, with multiple molecular events driving its pathogenesis. Patients with atypical CML had a low response to current therapies, with an overall response rate (ORR) of 33.3% to hypomethylating agent (HMA)-based therapy. The current treatment strategies, including hematopoietic stem cell transplantation (HSCT), did not improve overall survival (OS) in atypical CML patients, with a median survival of 20 months. Thus, the benefits from HSCT and candidates for HSCT remain to be further evaluated. Acute myeloid leukemia (AML)-like chemotherapy followed by bridging allogeneic HSCT may be an ideal regimen for suitable individuals. The large-scale and prospective clinical studies will help to address the dilemma.

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Deininger MWN, Tyner JW, Solary E (2017) Turning the tide in myelodysplastic/myeloproliferative neoplasms. Nat Rev Cancer 17:425–440. https://doi.org/10.1038/nrc.2017.40CrossRefPubMed

Palomo L, Acha P, Solé F (2021) Genetic aspects of myelodysplastic/myeloproliferative neoplasms. Cancers 13:2120. https://doi.org/10.3390/cancers13092120CrossRefPubMedPubMedCentral

Montalban-Bravo G, Kanagal-Shamanna R, Sasaki K et al (2021) Clinicopathologic correlates and natural history of atypical chronic myeloid leukemia. Cancer 127:3113–3124. https://doi.org/10.1002/cncr.33622CrossRefPubMed

Patnaik MM, Barraco D, Lasho TL et al (2017) Targeted next generation sequencing and identification of risk factors in World Health Organization defined atypical chronic myeloid leukemia. Am J Hematol 92:542–548. https://doi.org/10.1002/ajh.24722CrossRefPubMedPubMedCentral

Gotlib J, Maxson JE, George TI, Tyner JW (2013) The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment. Blood 122:1707–1711. https://doi.org/10.1182/blood-2013-05-500959CrossRefPubMedPubMedCentral

Piazza R, Valletta S, Winkelmann N et al (2013) Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nat Genet 45:18–24. https://doi.org/10.1038/ng.2495CrossRefPubMed

Khoury JD, Solary E, Abla O et al (2022) The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. https://doi.org/10.1038/s41375-022-01613-1CrossRefPubMedPubMedCentral

Savona MR, Malcovati L, Komrokji R et al (2015) An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. Blood 125:1857–1865. https://doi.org/10.1182/blood-2014-10-607341CrossRefPubMedPubMedCentral

Makishima H, Yoshida K, Nguyen N et al (2013) Somatic SETBP1 mutations in myeloid malignancies. Nat Genet 45:942–946. https://doi.org/10.1038/ng.2696CrossRefPubMedPubMedCentral

10.

Thol F, Suchanek KJ, Koenecke C et al (2013) SETBP1 mutation analysis in 944 patients with MDS and AML. Leukemia 27:2072–2075. https://doi.org/10.1038/leu.2013.145CrossRefPubMed

11.

Zhang H, Wilmot B, Bottomly D et al (2019) Genomic landscape of neutrophilic leukemias of ambiguous diagnosis. Blood 134:867–879. https://doi.org/10.1182/blood.2019000611CrossRefPubMedPubMedCentral

12.

Burd A, Levine RL, Ruppert AS et al (2020) Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial. Nat Med 26:1852–1858. https://doi.org/10.1038/s41591-020-1089-8CrossRefPubMedPubMedCentral

13.

Crisà E, Nicolosi M, Ferri V et al (2020) Atypical chronic myeloid leukemia: where are we now? Int J Mol Sci 21:6862. https://doi.org/10.3390/ijms21186862CrossRefPubMedPubMedCentral

14.

Palomo L, Meggendorfer M, Hutter S et al (2020) Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasmsomo. Blood 136:1851–1862. https://doi.org/10.1182/blood.2019004229CrossRefPubMedPubMedCentral

15.

Patnaik MM, Tefferi A (2022) Chronic myelomonocytic leukemia: 2022 update on diagnosis, risk stratification, and management. Am J Hematol 97:352–372. https://doi.org/10.1002/ajh.26455CrossRefPubMed

16.

Garcia-Manero G, Chien KS, Montalban-Bravo G (2020) Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management. Am J Hematol 95:1399–1420. https://doi.org/10.1002/ajh.25950CrossRefPubMed

17.

Tefferi A (2021) Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol 96:145–162. https://doi.org/10.1002/ajh.26050CrossRefPubMed

18.

Döhner H, Estey E, Grimwade D et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129:424–447. https://doi.org/10.1182/blood-2016-08-733196CrossRefPubMedPubMedCentral

19.

Martín-Izquierdo M, Abáigar M, Hernández-Sánchez JM, et al (2020) Co-occurrence of cohesin complex and Ras signaling mutations during progression from myelodysplastic syndromes to secondary acute myeloid leukemia. Haematologica 106. https://doi.org/10.3324/haematol.2020.248807

20.

Carr RM, Vorobyev D, Lasho T et al (2021) RAS mutations drive proliferative chronic myelomonocytic leukemia via a KMT2A-PLK1 axis. Nat Commun 12:2901. https://doi.org/10.1038/s41467-021-23186-wCrossRefPubMedPubMedCentral

21.

Elena C, Gallì A, Such E et al (2016) Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood 128:1408–1417. https://doi.org/10.1182/blood-2016-05-714030CrossRefPubMedPubMedCentral

22.

Patnaik MM, Tefferi A (2016) Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia. Blood Cancer J 6:e393–e393. https://doi.org/10.1038/bcj.2016.5CrossRefPubMedPubMedCentral

23.

DiFilippo EC, Coltro G, Carr RM et al (2020) Spectrum of abnormalities and clonal transformation in germline RUNX1 familial platelet disorder and a genomic comparative analysis with somatic RUNX1 mutations in MDS/MPN overlap neoplasms. Leukemia 34:2519–2524. https://doi.org/10.1038/s41375-020-0752-xCrossRefPubMed

24.

Taube F, Georgi JA, Kramer M et al (2022) CEBPA mutations in 4708 patients with acute myeloid leukemia: differential impact of bZIP and TAD mutations on outcome. Blood 139:87–103. https://doi.org/10.1182/blood.2020009680CrossRefPubMed

25.

Ball BJ, Famulare CA, Stein EM et al (2020) Venetoclax and hypomethylating agents (HMAs) induce high response rates in MDS, including patients after HMA therapy failure. Blood Adv 4:2866–2870. https://doi.org/10.1182/bloodadvances.2020001482CrossRefPubMedPubMedCentral

26.

Zeidan AM, Pollyea DA, Garcia JS et al (2019) A phase 1b study evaluating the safety and efficacy of venetoclax as monotherapy or in combination with azacitidine for the treatment of relapsed/refractory myelodysplastic syndrome. Blood 134:565–565. https://doi.org/10.1182/blood-2019-124994CrossRef

27.

Wei AH, Garcia JS, Borate U et al (2019) A phase 1b study evaluating the safety and efficacy of venetoclax in combination with azacitidine in treatment-naïve patients with higher-risk myelodysplastic syndrome. Blood 134:568–568. https://doi.org/10.1182/blood-2019-124437CrossRef

28.

Desikan SPP, Montalban-Bravo G, Ohanian M et al (2021) A phase I study of the combination of venetoclax and azacitidine in relapse/refractory higher risk myelodysplastic syndrome (MDS). Blood 138:3704–3704. https://doi.org/10.1182/blood-2021-153170CrossRef

29.

Bazinet A, Jabbour EJ, Kantarjian H et al (2021) A phase I/II study of venetoclax in combination with 5-azacytidine in treatment-naïve and relapsed/refractory high-risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML). Blood 138:535–535. https://doi.org/10.1182/blood-2021-153086CrossRef

30.

Dao KHT, Gotlib J, Deininger MMN et al (2020) Efficacy of ruxolitinib in patients with chronic neutrophilic leukemia and atypical chronic myeloid leukemia. J Clin Oncol 38:1006–1018. https://doi.org/10.1200/JCO.19.00895CrossRefPubMed

31.

Assi R, Kantarjian HM, Garcia-Manero G et al (2018) A phase II trial of ruxolitinib in combination with azacytidine in myelodysplastic syndrome/myeloproliferative neoplasms. Am J Hematol 93:277–285. https://doi.org/10.1002/ajh.24972CrossRefPubMed

32.

Gotlib J (2017) How I treat atypical chronic myeloid leukemia. Blood 129:838–845. https://doi.org/10.1182/blood-2016-08-693630CrossRefPubMed

33.

Talati C, Padron E (2016) An exercise in extrapolation: clinical management of atypical CML, MDS/MPN-unclassifiable, and MDS/MPN-RS-T. Curr Hematol Malig Rep 11:425–433. https://doi.org/10.1007/s11899-016-0350-1CrossRefPubMed

34.

Onida F, de Wreede LC, van Biezen A et al (2017) Allogeneic stem cell transplantation in patients with atypical chronic myeloid leukaemia: a retrospective study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation. Br J Haematol 177:759–765. https://doi.org/10.1111/bjh.14619CrossRefPubMed

Titel: Molecular genetics and management of world health organization defined atypical chronic myeloid leukemia
verfasst von: Yingxin Sun
Qinrong Wang
Xingxia Zhang
Zhiyu Zhang
Qian Wang
Jiannong Cen
Mingqing Zhu
Jinlan Pan
Dandan Liu
Depei Wu
Yifeng Cai
Suning Chen
Publikationsdatum: 03.02.2023
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 4/2023
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-023-05106-8

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