Abstract
Chronic myelomonocytic leukaemia (CMML) is a clonal disorder of the haematopoietic stem cell characterised by the presence of an absolute monocytosis in peripheral blood. The disease carries myelodysplastic and myeloproliferative features. This dilemma was sought to be overcome by the World Health Organization (WHO) in 2001, when CMML was classified within a new category of myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN). The identification of molecular markers in patients with CMML has dramatically increased over the past couple of years. However, the impact on prognosis and therapeutic interventions needs to be defined. Testing of new agents in the setting of CMML proves to be difficult due to limited number of patients. This review has a focus on current diagnosis including new molecular data and treatment of CMML.
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References
Vardiman JW, Pierre R, Bain B, Bennett JM, Imbert M, Brunning RD, et al. WHO histological classification of myelodysplastic/myeloproliferative diseases. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization classification of tumours: tumours of the haematopoietic and lympoid tissues. Lyon: International Agency for Research on Cancer (IARC) Press; 2001. pp. 47–59.
Kern W, Bacher U, Haferlach C, Schnittger S, Haferlach T. Acute monoblastic/monocytic leukemia and chronic myelomonocytic leukemia share common immunophenotypic features but differ in the extent of aberrantly expressed antigens and amount of granulocytic cells. Leuk Lymphoma. 2011;52:92–100.
Subira D, Font P, Villalon L, Serrano C, Askari E, Gongora E, et al. Immonophenotype in chronic myelomonocytic leukemia: is it closer to myelodysplastic syndromes or to myeloproliferative disorders? Transl Res. 2008;151:240–5.
Gorczyca W. Flow cytometry immunophenotypic characteristics of monocytic population in acute monocytic leukaemia (AML-M5), acute myelomonocytic leukaemia (AML-M4), and chronic myelomonocytic leukaemia (CMML). Methods Cell Biol. 2004;75:665–7.
Xu Y, McKenna RW, Karandikar NJ, Pildain AJ, Kroft SH. Flow cytometric analysis of monocytes as a tool for distinguishing chronic myelomonocytic leukemia from reactive monocytosis. Am J Clin Pathol. 2005;124:799–806.
Vardiman JW, Imbert M, Pierre R, Brunning RD, Bain B, Flandrin G, et al. Chronic myelomonocytic leukaemia. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization classification of tumors: pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press; 2001. pp. 49–52.
Orazi A, Chiu R, O’Malley DP, Czader M, Allen SL, An C, Vance GH. Chronic myelomonocytic leukemia: the role of bone marrow biopsy immunohistolog. Mod Pathol. 2006;19:1536–45.
Germing U, Gattermann N, Minning H, Heyll A, Aul C. Problems in the classification of CMML-dysplastic versus proliferative type. Leuk Res. 1998;22:871–8.
Fenaux P, Beuscart R, Lai JL, Jouet JP, Bauters F. Prognostic factors in adult chronic myelomonocytic leukemia: an analysis of 107 cases. J Clin Oncol. 1988;6:1417–24.
Storniolo AM, Moloney WC, Rosenthal DS, Cox C, Bennett JM. Chronic myelomonocytic leukemia. Leukemia. 1990;4:766–70.
McClure RF, Dewald GW, Hoyer JK, Hanson CA. Isolated isochromosome 17q: a distinct type of mixed myeloproliferative disorder/myelodysplastic syndrome with an aggressive clinical course. Br J Haematol. 1999;106:445–54.
Burgstaller S, Reiter A, Cross NCP. BCR-ABL negative chronic myeloid leukemia. Curr Hem Malignancy Rep. 2007;2:75–82.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–51.
Kosmider O, Gelsi-Bayer V, Ciudad M, Racoeur C, Jooste V, Vey N, et al. TET2 gene mutationis a frequent and adverse event in chronic myelomonocytic leukemia. Haematologica. 2009;94:1676–81.
Kohlmann A, Grossmann V, Klein H, Schindela S, Weiss T, Kazak B, et al. Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1. J Clin Oncol. 2010;28:3858–65.
Dunbar AJ, Gondek LP, O’Keefe CL, Makishima H, Rataul MS, Szpurka H, et al. 250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies. Cancer Res. 2008;68:10349–57.
Ricci C, Fermo E, Corti S, Molteni M, Faricciotti A, Cortelezzi A, et al. RAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant. Clin Cancer Res. 2010;16:2246–56.
Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zahng L, et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood. 2005;106:2162–8.
Pich A, Riera L, Sismondi F, Godio L, Davico Bonino L, Marmont F, Francia di Celle P. JAK2V617F activating mutation is associated with the myeloproliferative type of chronic myelomonocytic leukaemia. J Clin Pathol. 2009;62:798–801.
Grand FH, Hidalgo-Curtis CE, Ernst T, Zoi K, Zoi C, McGuire C, et al. Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood. 2009;113:6182–92.
Gelsi-Boyer V, Trouplin V, Adelaide J, Aceto N, Remy V, Pinson S, et al. Genome profiling of chronic myelomonoytic leukemia: frequent alterations of RAS and RUNX1 genes. BMC Cancer. 2008;8:299.
Kuo MC, Liang DC, Huang CF, Shih YS, Wu JH, Lin TL, Shih LY. RUNX1 mutations are frequent in chronic myelomonocytic leukemia and mutations at the C-terminal region might predict acute myeloid leukemia transformation. Leukemia. 2009;23:1426–31.
Gelsi-Boyer V, Trouplin V, Adelaide J, Bonansea J, Cervera N, Carbuccia N, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndrome and chronic myelomonocytic leukaemia. Br J Haematol. 2009;145:788–800.
Germing U, Kündgen A, Gattermann N. Risk assessment in chronic myelomonocytic leukemia (CMML). Leuk Lymphoma. 2004;45:1311–8.
Molica S, Iannaccuro P, Albeti A. Chronic myelomonocytic leukemia: a test of a proposed staging system. Am J Haematol. 1990;35:129–30.
Worsley A, Oscier DG, Stevens J, Darlow S, Figes A, Mufti GJ, Hamblin TJ. Prognostic features of chronic myelomonocytic leukemia: a modified Bournemouth score gives the best prediction of survival. Br J Haematol. 1988;68:17–21.
Aul C, Ganttermann N, Neyll A, Germing U, Gerigs G, Schneider W. Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia. 1992;6:52–9.
Gonzales-Medina I, Bueno J, Torrequebrada A, Lopez A, Vallespi T, Massague I. Two groups of chronic myelomonocytic leukemia: myelodysplastic and myeloproliferative. Prognostic implications in a series of a single center. Leuk Res. 2002;26:821–4.
Onida F, Kantarjian HM, Smith TL, Ball G, Keating MJ, Estey EH, et al. Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. Blood. 2002; 99: 840–9.
Beran M, Wen S, Shen Y, Onida F, Jelinek J, Cortes J, et al. Prognostic factors and risk assessment in chronic myelomonocytic leukemia: validation study of the M.D. Anderson Prognositc Scoring System. Leuk Lymphoma. 2007;48:1150–60.
Wattel E, Guerci A, Hecquet B, Economopoulos T, Copplestone A, Mahe B, et al. A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Blood. 1996;88:2480–7.
Beran M, Estey E, O’Brien S, Giles FJ, Koller CA, Kornblau S, et al. Results of topotecan single-agent therapy in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk lymphoma. 1998;31:521–31.
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–32.
Wong E, Seymour JF, Kenealy M, Westerman D, Herbert K, Dickinson M. Treatment of chronic myelomonocytic leukemia with azacitidine. Leuk Lymphoma. 2012. Epub ahead of print.
Feldman E, Cortes J, DeAngelo DJ, Holyoake T, Simonsson B, O’Brien SG, et al. On the use of lonafarnib in myelodysplastic syndrome and chronic myelomonocytic leukemia. Leukemia. 2008;22:1707–11.
Sliitonen T, Timonen T, Juvonen E, Terävä V, Kutila A, Honkanen T, et al. Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes. Haematologica. 2007;92:1119–22.
Eissa H, Gooley TA, Sorror ML, Nguyen F, Scott BL, Doney K, et al. Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia: relapse-free survival is determined by karyotype and comorbidities. Biol Blood Marrow Transpl. 2010. doi:10.1016/j.bbmt.2010.09.018.
Conflict of interest
The author declares that there is no actual or potential conflict of interest in relation to this article.