Acute megakaryoblastic leukaemia shows high frequency of chromosome 1q aberrations and dismal outcome.
AMKL
AML
AML M7
allo-HSCT
cytogenetic and molecular landscape
prognosis
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
revised:
04
07
2023
received:
15
04
2023
accepted:
05
07
2023
medline:
12
9
2023
pubmed:
17
7
2023
entrez:
17
7
2023
Statut:
ppublish
Résumé
Acute megakaryoblastic leukaemia (AMKL) is associated with poor prognosis. Limited information is available on its cytogenetics, molecular genetics and clinical outcome. We performed genetic analyses, evaluated prognostic factors and the value of allogeneic haematopoietic stem cell transplantation (allo-HSCT) in a homogenous adult AMKL patient cohort. We retrospectively analysed 38 adult patients with AMKL (median age: 58 years, range: 21-80). Most received intensive treatment in AML Cooperative Group (AMLCG) trials between 2001 and 2016. Cytogenetic data showed an accumulation of adverse risk markers according to ELN 2017 and an unexpected high frequency of structural aberrations on chromosome arm 1q (33%). Most frequently, mutations occurred in TET2 (23%), TP53 (23%), JAK2 (19%), PTPN11 (19%) and RUNX1 (15%). Complete remission rate in 33 patients receiving intensive chemotherapy was 33% and median overall survival (OS) was 33 weeks (95% CI: 21-45). Patients undergoing allo-HSCT (n = 14) had a superior median OS (68 weeks; 95% CI: 11-126) and relapse-free survival (RFS) of 27 weeks (95% CI: 4-50), although cumulative incidence of relapse after allo-HSCT was high (62%). The prognosis of AMKL is determined by adverse genetic risk factors and therapy resistance. So far allo-HSCT is the only potentially curative treatment option in this dismal AML subgroup.
Banques de données
ClinicalTrials.gov
['NCT01382147']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1165-1177Informations de copyright
© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
Références
Tallman MS, Neuberg D, Bennett JM, Francois CJ, Paietta E, Wiernik PH, et al. Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group experience. Blood. 2000 Oct 1;96(7):2405-2411. Epub 2000 Sep 26. PMID 11001891.
Gruber TA, Downing JR. The biology of pediatric acute megakaryoblastic leukemia. Blood. 2015 Aug 20;126(8):943-949. https://doi.org/10.1182/blood-2015-05-567859. Epub 2015 Jul 19. PMID 26186939.
de Rooij JD, Branstetter C, Ma J, Li Y, Walsh MP, Cheng J, et al. Pediatric non-down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. Nat Genet. 2017 Mar;49(3):451-456. https://doi.org/10.1038/ng.3772. Epub 2017 Jan 24. PMID 28112737.
Hahn AW, Li B, Prouet P, Giri S, Pathak R, Martin MG. Acute megakaryocytic leukemia: what have we learned. Blood Rev. 2016 Jan;30(1):49-53. https://doi.org/10.1016/j.blre.2015.07.005. Epub 2015 Aug 01. PMID 26228843.
Oki Y, Kantarjian HM, Zhou X, Cortes J, Faderl S, Verstovsek S, et al. Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center. Blood. 2006 Feb 1;107(3):880-884. https://doi.org/10.1182/blood-2005-06-2450. Epub 2005 Aug 27. PMID 16123215.
Pagano L, Pulsoni A, Vignetti M, Mele L, Fianchi L, Petti MC, et al. Acute megakaryoblastic leukemia: experience of GIMEMA trials. Leukemia. 2002 Sep;16(9):1622-1626. https://doi.org/10.1038/sj.leu.2402618. Epub 2002 Aug 30. PMID 12200673.
Duchayne E, Fenneteau O, Pages MP, Sainty D, Arnoulet C, Dastugue N, et al. Acute megakaryoblastic leukaemia: a national clinical and biological study of 53 adult and childhood cases by the Groupe Francais d'Hematologie Cellulaire (GFHC). Leuk Lymphoma. 2003 Jan;44(1):49-58. https://doi.org/10.1080/1042819021000040279. Epub 2003 Apr 15. PMID 12691142.
Giri S, Pathak R, Prouet P, Li B, Martin MG. Acute megakaryocytic leukemia is associated with worse outcomes than other types of acute myeloid leukemia. Blood. 2014 Dec 11;124(25):3833-3834. https://doi.org/10.1182/blood-2014-09-603415. Epub 2014 Dec 17. PMID 25498456.
Buchner T, Berdel WE, Schoch C, Haferlach T, Serve HL, Kienast J, et al. Double induction containing either two courses or one course of high-dose cytarabine plus mitoxantrone and postremission therapy by either autologous stem-cell transplantation or by prolonged maintenance for acute myeloid leukemia. J Clin Oncol. 2006 Jun 1;24(16):2480-2489. https://doi.org/10.1200/JCO.2005.04.5013. Epub 2006 Jun 01. PMID 16735702.
Braess J, Spiekermann K, Staib P, Gruneisen A, Wormann B, Ludwig WD, et al. Dose-dense induction with sequential high-dose cytarabine and mitoxantone (S-HAM) and pegfilgrastim results in a high efficacy and a short duration of critical neutropenia in de novo acute myeloid leukemia: a pilot study of the AMLCG. Blood. 2009 Apr 23;113(17):3903-3910. https://doi.org/10.1182/blood-2008-07-162842. Epub 2009 Jan 10. PMID 19131552.
Braess J, Amler S, Kreuzer KA, Spiekermann K, Lindemann HW, Lengfelder E, et al. Sequential high-dose cytarabine and mitoxantrone (S-HAM) versus standard double induction in acute myeloid leukemia-a phase 3 study. Leukemia. 2018 Dec;32(12):2558-2571. https://doi.org/10.1038/s41375-018-0268-9. Epub 2018 Oct 03. PMID 30275528.
Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005 Aug;90(8):1128-1132. Epub 2005 Aug 05. PMID 16079113.
Metzeler KH, Herold T, Rothenberg-Thurley M, Amler S, Sauerland MC, Gorlich D, et al. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016 Aug 4;128(5):686-698. https://doi.org/10.1182/blood-2016-01-693879. Epub 2016 Jun 12. PMID 27288520.
Kiyoi H, Naoe T, Yokota S, Nakao M, Minami S, Kuriyama K, et al. Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho). Leukemia. 1997 Sep;11(9):1447-1452. https://doi.org/10.1038/sj.leu.2400756. Epub 1997 Sep 26. PMID 9305596.
R Development Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2017.
Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010 Jul 22;116(3):354-365. https://doi.org/10.1182/blood-2009-11-254441. Epub 2010 Apr 14. PMID 20385793.
Forlenza CJ, Zhang Y, Yao J, Benayed R, Steinherz P, Ramaswamy K, et al. A case of KMT2A-SEPT9 fusion-associated acute megakaryoblastic leukemia. Cold Spring Harb Mol Case Stud. 2018 Dec 17;4(6):a003426. https://doi.org/10.1101/mcs.a003426. Epub 2018 Nov 21. PMID 30455225.
Bahar B, Barton K, Kini AR. The role of the exon 13 G571S JAK2 mutation in myeloproliferative neoplasms. Leuk Res Rep. 2016;6:27-28. https://doi.org/10.1016/j.lrr.2016.07.003. Epub 2016 Dec 08. PMID 27924280.
Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26;129(4):424-447. https://doi.org/10.1182/blood-2016-08-733196. Epub 2016 Nov 30. PMID 27895058.
Krug U, Berdel WE, Gale RP, Haferlach C, Schnittger S, Muller-Tidow C, et al. Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia. Leukemia. 2016 Jun;30(6):1230-1236. https://doi.org/10.1038/leu.2016.25. Epub 2016 Feb 10. PMID 26859081.
Yoshida K, Toki T, Okuno Y, Kanezaki R, Shiraishi Y, Sato-Otsubo A, et al. The landscape of somatic mutations in down syndrome-related myeloid disorders. Nat Genet. 2013 Nov;45(11):1293-1299. https://doi.org/10.1038/ng.2759. Epub 2013 Sep 24. PMID 24056718.
Schweitzer J, Zimmermann M, Rasche M, von Neuhoff C, Creutzig U, Dworzak M, et al. Improved outcome of pediatric patients with acute megakaryoblastic leukemia in the AML-BFM 04 trial. Ann Hematol. 2015 Aug;94(8):1327-1336. https://doi.org/10.1007/s00277-015-2383-2. Epub 2015 Apr 29. PMID 25913479.
Gruber TA, Larson Gedman A, Zhang J, Koss CS, Marada S, Ta HQ, et al. An Inv(16)(p13.3q24.3)-encoded CBFA2T3-GLIS2 fusion protein defines an aggressive subtype of pediatric acute megakaryoblastic leukemia. Cancer Cell. 2012 Nov 13;22(5):683-697. https://doi.org/10.1016/j.ccr.2012.10.007. Epub 2012 Nov 17. PMID 23153540.
de Rooij JD, Hollink IH, Arentsen-Peters ST, van Galen JF, Berna Beverloo H, Baruchel A, et al. NUP98/JARID1A is a novel recurrent abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern. Leukemia. 2013 Dec;27(12):2280-2288. https://doi.org/10.1038/leu.2013.87. Epub 2013 Mar 28. PMID 23531517.
Caramazza D, Hussein K, Siragusa S, Pardanani A, Knudson RA, Ketterling RP, et al. Chromosome 1 abnormalities in myeloid malignancies: a literature survey and karyotype-phenotype associations. Eur J Haematol. 2010 Mar;84(3):191-200. https://doi.org/10.1111/j.1600-0609.2009.01392.x. Epub 2009 Dec 17. PMID 20002154.
Zhang T, Xu Y, Pan J, Li H, Wang Q, Wen L, et al. High frequency of RUNX1 mutation in myelodysplastic syndrome patients with whole-arm translocation of der(1;7)(q10;p10). Leukemia. 2017 Oct;31(10):2257-2260. https://doi.org/10.1038/leu.2017.228. Epub 2017 Jul 20. PMID 28720763.
Forestier E, Izraeli S, Beverloo B, Haas O, Pession A, Michalova K, et al. Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with down syndrome: an iBFM-SG study. Blood. 2008 Feb 1;111(3):1575-1583. https://doi.org/10.1182/blood-2007-09-114231. Epub 2007 Nov 01. PMID 17971484.
Blink M, Zimmermann M, von Neuhoff C, Reinhardt D, de Haas V, Hasle H, et al. Normal karyotype is a poor prognostic factor in myeloid leukemia of down syndrome: a retrospective, international study. Haematologica. 2014 Feb;99(2):299-307. https://doi.org/10.3324/haematol.2013.089425. Epub 2013 Aug 13. PMID 23935021.
Silva ML, Pombo-de-Oliveira MS, Raimondi SC, Mkrtchyan H, Abdelhay E, de Figueiredo AF, et al. Unbalanced chromosome 1 abnormalities leading to partial trisomy 1q in four infants with down syndrome and acute megakaryocytic leukemia. Mol Cytogenet. 2009 Feb 19;2:7. https://doi.org/10.1186/1755-8166-2-7. Epub 2009 Feb 21. PMID 19228396.
Hama A, Muramatsu H, Makishima H, Sugimoto Y, Szpurka H, Jasek M, et al. Molecular lesions in childhood and adult acute megakaryoblastic leukaemia. Br J Haematol. 2012 Feb;156(3):316-325. https://doi.org/10.1111/j.1365-2141.2011.08948.x. Epub 2011 Nov 30. PMID 22122069.
Moassass F, Wafa A, Liehr T, Al-Ablog A, Al AW. Down syndrome associated childhood myeloid leukemia with yet unreported acquired chromosomal abnormalities and a new potential adverse marker: dup(1)(q25q44). Mol Cytogenet. 2018;11:22. https://doi.org/10.1186/s13039-018-0370-8. Epub 2018 Mar 23. PMID 29563973.
Sondka Z, Bamford S, Cole CG, Ward SA, Dunham I, Forbes SA. The COSMIC cancer gene census: describing genetic dysfunction across all human cancers. Nat Rev Cancer. 2018 Nov;18(11):696-705. https://doi.org/10.1038/s41568-018-0060-1. Epub 2018 Oct 08. PMID 30293088.
Institute WS. Cancer gene census. COSMIC. Available from: https://cancer.sanger.ac.uk/cosmic/census?tier=1
Imbert M, Nguyen D, Sultan C. Myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML) with myelofibrosis. Leuk Res. 1992;16(1):51-54. https://doi.org/10.1016/0145-2126(92)90100-l. Epub 1992 Jan 01. PMID 1732672.
Papadantonakis N, Matsuura S, Ravid K. Megakaryocyte pathology and bone marrow fibrosis: the lysyl oxidase connection. Blood. 2012 Aug 30;120(9):1774-1781. https://doi.org/10.1182/blood-2012-02-402594. Epub 2012 Jul 07. PMID 22767499.
Wen Q, Goldenson B, Silver SJ, Schenone M, Dancik V, Huang Z, et al. Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL. Cell. 2012 Aug 3;150(3):575-589. https://doi.org/10.1016/j.cell.2012.06.032. Epub 2012 Aug 07. PMID 22863010.
Gangat N, Marinaccio C, Swords R, Watts JM, Gurbuxani S, Rademaker A, et al. Aurora kinase a inhibition provides clinical benefit, normalizes megakaryocytes, and reduces bone marrow fibrosis in patients with myelofibrosis: a phase I trial. Clin Cancer Res. 2019 Aug 15;25(16):4898-4906. https://doi.org/10.1158/1078-0432.CCR-19-1005. Epub 2019 May 08. PMID 31061068.
Brunner AM, Blonquist TM, DeAngelo DJ, McMasters M, Fell G, Hermance NM, et al. Alisertib plus induction chemotherapy in previously untreated patients with high-risk, acute myeloid leukaemia: a single-arm, phase 2 trial. Lancet Haematol. 2020 Feb;7(2):e122-e133. https://doi.org/10.1016/S2352-3026(19)30203-0. Epub 2019 Dec 16. PMID 31837959.
Grimm J, Bhayadia R, Gack L, Heckl D, Klusmann JH. Combining LSD1 and JAK-STAT inhibition targets down syndrome-associated myeloid leukemia at its core. Leukemia. 2022 Jul;36(7):1926-1930. https://doi.org/10.1038/s41375-022-01603-3. Epub 2022 May 25. PMID 35610347.
Labuhn M, Perkins K, Matzk S, Varghese L, Garnett C, Papaemmanuil E, et al. Mechanisms of progression of myeloid preleukemia to transformed myeloid leukemia in children with down syndrome. Cancer Cell. 2019 Aug 12;36(2):123-138 e10. https://doi.org/10.1016/j.ccell.2019.06.007. Epub 2019 Jul 16. PMID 31303423.
Kuusanmaki H, Dufva O, Vaha-Koskela M, Leppa AM, Huuhtanen J, Vanttinen I, et al. Erythroid/megakaryocytic differentiation confers BCL-XL dependency and venetoclax resistance in acute myeloid leukemia. Blood. 2023 Mar 30;141(13):1610-1625. https://doi.org/10.1182/blood.2021011094. Epub 2022 Dec 13. PMID 36508699.