Chronic Myelomonocytic Leukemia and Atypical Chronic Myeloid Leukemia: Novel Pathogenetic Lesions

Overview

Journal Semin Oncol

Specialty Oncology

Date 2012 Feb 1

PMID 22289493

Citations 13

Authors

Hideki Muramatsu

Hideki Makishima

Jaroslaw P Maciejewski

Affiliations

Soon will be listed here.

Abstract

Chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML) are distinct, yet related, entities of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) characterized by morphologic dysplasia with accumulation of monocytes or neutrophils, respectively. Our understanding of the molecular pathogenesis of CMML and aCML has advanced, mainly due to the application of novel technologies such as array-based karyotyping and next-generation sequencing. In addition to previously known recurrent aberrations, somatic uniparental disomy affecting chromosomes 3, 4, 7, and 11 frequently occurs in CMML. Novel somatic mutations of genes, including those associated with proliferation signaling (CBL, RAS, RUNX1, JAK2 (V617F)) and with modification of epigenetic status (TET2, ASXL1, UTX, EZH2) have been found. Various combinations of mutations suggest a multistep pathogenesis and may account for clinical heterogeneity. Most recently, several spliceosome-associated-gene mutations were reported and SRSF2 mutations are frequently detected in CMML. The prognostic and diagnostic significance of these molecular lesions, in particular their value as biomarkers of response or resistance to specific therapies, while uncertain now is likely to be clarified as large systematic studies come to completion.

Citing Articles

Mutational landscape of chronic myelomonocytic leukemia and its potential clinical significance.

Han W, Zhou F, Wang Z, Hua H, Qin W, Jia Z Int J Hematol. 2021; 115(1):21-32.

PMID: 34449040 DOI: 10.1007/s12185-021-03210-x.

Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia.

Dao K, Tyner J, Gotlib J Curr Hematol Malig Rep. 2017; 12(5):432-441.

PMID: 28983816 DOI: 10.1007/s11899-017-0413-y.

Structural and functional analyses of the spliceosome requires a multi-disciplinary approach.

Ohi M Methods. 2017; 125:1-2.

PMID: 28780959 PMC: 5881893. DOI: 10.1016/j.ymeth.2017.07.022.

CBL family E3 ubiquitin ligases control JAK2 ubiquitination and stability in hematopoietic stem cells and myeloid malignancies.

Lv K, Jiang J, Donaghy R, Riling C, Cheng Y, Chandra V Genes Dev. 2017; 31(10):1007-1023.

PMID: 28611190 PMC: 5495118. DOI: 10.1101/gad.297135.117.

JAK2 V617F Mutation in Adult T Cell Leukemia-Lymphoma.

Ayatollahi H, Sadeghian M, Keramati M, Karimiani E, Jafarian A, Shirdel A Indian J Hematol Blood Transfus. 2016; 32(4):437-441.

PMID: 27812253 PMC: 5074958. DOI: 10.1007/s12288-015-0620-4.

References

Baxter E, Scott L, Campbell P, East C, Fourouclas N, Swanton S . Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005; 365(9464):1054-61. DOI: 10.1016/S0140-6736(05)71142-9. View

Dang L, White D, Gross S, Bennett B, Bittinger M, Driggers E . Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009; 462(7274):739-44. PMC: 2818760. DOI: 10.1038/nature08617. View

Sheng X, Kawamura M, Ohnishi H, Ida K, Hanada R, Kojima S . Mutations of the RAS genes in childhood acute myeloid leukemia, myelodysplastic syndrome and juvenile chronic myelocytic leukemia. Leuk Res. 1997; 21(8):697-701. DOI: 10.1016/s0145-2126(97)00036-2. View

Tahiliani M, Koh K, Shen Y, Pastor W, Bandukwala H, Brudno Y . Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009; 324(5929):930-5. PMC: 2715015. DOI: 10.1126/science.1170116. View

Lee S, Cho Y, Na J, Park U, Kang M, Kim E . ASXL1 represses retinoic acid receptor-mediated transcription through associating with HP1 and LSD1. J Biol Chem. 2009; 285(1):18-29. PMC: 2804164. DOI: 10.1074/jbc.M109.065862. View

Loh M, Reynolds M, Vattikuti S, Gerbing R, Alonzo T, Carlson E . PTPN11 mutations in pediatric patients with acute myeloid leukemia: results from the Children's Cancer Group. Leukemia. 2004; 18(11):1831-4. DOI: 10.1038/sj.leu.2403492. View

Turner B, Eves T, Refaeli Y . Small-molecule inhibitors of Bcl-2 family proteins are able to induce tumor regression in a mouse model of pre-B-cell acute lymphocytic lymphoma. DNA Cell Biol. 2008; 27(3):133-42. DOI: 10.1089/dna.2007.0675. View

Delhommeau F, Dupont S, Valle V, James C, Trannoy S, Masse A . Mutation in TET2 in myeloid cancers. N Engl J Med. 2009; 360(22):2289-301. DOI: 10.1056/NEJMoa0810069. View

Sugimoto Y, Muramatsu H, Makishima H, Prince C, Jankowska A, Yoshida N . Spectrum of molecular defects in juvenile myelomonocytic leukaemia includes ASXL1 mutations. Br J Haematol. 2010; 150(1):83-7. DOI: 10.1111/j.1365-2141.2010.08196.x. View

10.

Abdel-Wahab O, Mullally A, Hedvat C, Garcia-Manero G, Patel J, Wadleigh M . Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies. Blood. 2009; 114(1):144-7. PMC: 2710942. DOI: 10.1182/blood-2009-03-210039. View

11.

Grand F, Hidalgo-Curtis C, Ernst T, Zoi K, Zoi C, McGuire C . Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood. 2009; 113(24):6182-92. DOI: 10.1182/blood-2008-12-194548. View

12.

LeMaistre A, Kantarjian H, Talpaz M, Cork A, Freireich E, Trujillo J . RAS mutations are rare events in Philadelphia chromosome-negative/bcr gene rearrangement-negative chronic myelogenous leukemia, but are prevalent in chronic myelomonocytic leukemia. Blood. 1990; 76(6):1214-9. View

13.

Mohamedali A, Smith A, Gaken J, Lea N, Mian S, Westwood N . Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome. J Clin Oncol. 2009; 27(24):4002-6. DOI: 10.1200/JCO.2009.22.6985. View

14.

Gross S, Cairns R, Minden M, Driggers E, Bittinger M, Jang H . Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. J Exp Med. 2010; 207(2):339-44. PMC: 2822606. DOI: 10.1084/jem.20092506. View

15.

Levine R, Loriaux M, Huntly B, Loh M, Beran M, Stoffregen E . The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. Blood. 2005; 106(10):3377-9. PMC: 1895066. DOI: 10.1182/blood-2005-05-1898. View

16.

Gondek L, Dunbar A, Szpurka H, McDevitt M, Maciejewski J . SNP array karyotyping allows for the detection of uniparental disomy and cryptic chromosomal abnormalities in MDS/MPD-U and MPD. PLoS One. 2007; 2(11):e1225. PMC: 2075364. DOI: 10.1371/journal.pone.0001225. View

17.

Martiat P, Michaux J, Rodhain J . Philadelphia-negative (Ph-) chronic myeloid leukemia (CML): comparison with Ph+ CML and chronic myelomonocytic leukemia. The Groupe Français de Cytogénétique Hématologique. Blood. 1991; 78(1):205-11. View

18.

Hernandez J, Del Canizo M, Cuneo A, Garcia J, Gutierrez N, Gonzalez M . Clinical, hematological and cytogenetic characteristics of atypical chronic myeloid leukemia. Ann Oncol. 2000; 11(4):441-4. DOI: 10.1023/a:1008393002748. View

19.

Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P . Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. 2002; 298(5595):1039-43. DOI: 10.1126/science.1076997. View

20.

Hirai H, Tanaka S, Azuma M, Anraku Y, Kobayashi Y, Fujisawa M . Transforming genes in human leukemia cells. Blood. 1985; 66(6):1371-8. View