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Chapter 11 - Myelodysplastic/Myeloproliferative Neoplasms

Published online by Cambridge University Press:  12 November 2020

Jon van der Walt ,
Attilio Orazi  and
Daniel A. Arber
By
Julia Geyer  and
Attilio Orazi
Jon van der Walt
Affiliation:
St Thomas’ Hospital, London
Attilio Orazi
Affiliation:
Texas Tech University
Daniel A. Arber
Affiliation:
University of Chicago
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Summary

The myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are clonal myeloid neoplasms characterized at the time of their initial presentation by the simultaneous presence of myelodysplastic and myeloproliferative features, which prevent them from being classified as either myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN). The incidence of MDS/MPN is estimated at 0.1 to 3/100,000 individuals. They are characterized by hypercellular bone marrow (BM) morphology due to proliferation in one or more of the myeloid lineages. Cytopaenias and dysplastic changes of any cell line may be seen in conjunction with elevated white blood cell (WBC) counts, thrombocytosis and organomegaly, features more commonly associated with MPN. Hepatosplenomegaly is frequently seen. The most common entities within the MDS/MPN group include chronic myelomonocytic leukaemia (CMML), atypical chronic myeloid leukaemia BCR-ABL1 negative (aCML) and juvenile myelomonocytic leukaemia (JMML), which is seen exclusively in paediatric patients. A less well-defined group of MDS/MPN-like diseases includes MDS/MPN unclassifiable (MDS/MPN-U) and a recently recognized entity of MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), previously known as refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T). It was considered a provisional entity within the group of MDS/MPN-U in the 2008 edition of the WHO, but has now been promoted to a true entry in the updated 2016 WHO edition. Since the publication of the last WHO Classification in 2008, multiple studies have examined the molecular pathogenetic features of the MDS/MPN entities (see Table 11.1). Many of these results have been incorporated into the updated 2016 WHO classification.

Keywords

Myelodysplasticmyeloproliferativeneoplasmmonocytosis myelomonocyticchronicatypicaljuvenilesideroblaststhrombocytosis
Type
Chapter
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Diagnostic Bone Marrow Haematopathology , pp. 162 - 180
Publisher: Cambridge University Press
Print publication year: 2021

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References

Rollison, DE, Howlader, N, Smith, MT, et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001–2004, using data from the NAACCR and SEER programs. Blood. 2008;112:45–52.CrossRefGoogle ScholarPubMed
McQuilten, ZK, Wood, EM, Polizzotto, MN, et al. Underestimation of myelodysplastic syndrome incidence by cancer registries: results from a population-based data linkage study. Cancer. 2014;120:1686–94.Google Scholar
Swerdlow, SH, Campo, E, Harris, NL, et al. (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edn. Lyon: IARC; 2017.Google Scholar
Tefferi, A, Hoagland, HC, Therneau, TM, et al. Chronic myelomonocytic leukemia: natural history and prognostic determinants. Mayo Clin Proc. 1989;64:1246–54.Google Scholar
Peker, D, Padron, E, Bennett, JM, et al. A close association of autoimmune-mediated processes and autoimmune disorders with chronic myelomonocytic leukemia: observation from a single institution. Acta Haematol. 2015;133:249–56.Google Scholar
Grignano, E, Mekinian, A, Braun, T, et al. Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: a series of 26 cases and literature review. Leuk Res. 2016;47:136–41.CrossRefGoogle ScholarPubMed
Germing, U, Gattermann, N, Minning, H, et al. Problems in the classification of CMML--dysplastic versus proliferative type. Leuk Res. 1998;22:871–8.Google Scholar
Geyer, JT, Tam, W, Liu, YC, et al. Oligomonocytic chronic myelomonocytic leukemia (chronic myelomonocytic leukemia without absolute monocytosis) displays a similar clinicopathologic and mutational profile to classical chronic myelomonocytic leukemia. Mod Pathol. 2017;30:1213–22.Google Scholar
Valent, P, Orazi, A, Savona, MR, et al. Proposed diagnostic criteria for classical chronic myelomonocytic leukemia (CMML), CMML variants and pre-CMML conditions. Haematologica. 2019 Oct;104(10):1935–49.Google Scholar
Kouides, PA, Bennett, JM. Morphology and classification of the myelodysplastic syndromes and their pathologic variants. Semin Hematol. 1996;33:95–110.Google Scholar
Michaux, JL, Martiat, P. Chronic myelomonocytic leukaemia (CMML): a myelodysplastic or myeloproliferative syndrome? Leuk Lymphoma. 1993;9:35–41.CrossRefGoogle ScholarPubMed
Orazi, A, Chiu, R, O’Malley, DP, et al. Chronic myelomonocytic leukemia: the role of bone marrow biopsy immunohistology. Mod Pathol. 2006;19:1536–45.Google Scholar
Steensma, DP, Tefferi, A, Li, CY. Splenic histopathological patterns in chronic myelomonocytic leukemia with clinical correlations: reinforcement of the heterogeneity of the syndrome. Leuk Res. 2003;27:775–82.Google Scholar
Kraus, MD, Bartlett, NL, Fleming, MD, et al. Splenic pathology in myelodysplasia: a report of 13 cases with clinical correlation. Am J Surg Pathol. 1998;22:1255–66.CrossRefGoogle ScholarPubMed
O'Malley, DP, Kim, YS, Perkins, SL, et al. Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders. Mod Pathol. 2005;18:1550–61.Google Scholar
Pont, V, Miquel, FJ, Grau, TC, et al. Skin involvement in chronic myelomonocytic leukaemia as a predictor of transformation into acute myeloid leukaemia. J Eur Acad Dermatol and Venereol. 2001;15:260–2.Google Scholar
Duguid, JK, Mackie, MJ, McVerry, BA. Skin infiltration associated with chronic myelomonocytic leukaemia. Br J Haematol. 1983;53:257–64.Google Scholar
Mathew, RA, Bennett, JM, Liu, JJ, et al. Cutaneous manifestations in CMML: indication of disease acceleration or transformation to AML and review of the literature. Leuk Res. 2012;36:72–80.Google Scholar
Vitte, F, Fabiani, B, Benet, C, et al. Specific skin lesions in chronic myelomonocytic leukemia: a spectrum of myelomonocytic and dendritic cell proliferations: a study of 42 cases. Am J Surg Pathol. 2012;36:1302–16.CrossRefGoogle ScholarPubMed
Dunphy, CH. Comparative analysis of detecting monocytic cells and their aberrancy. Appl Immunohistochem Mol Morphol. 2011;19:336–40.Google Scholar
Selimoglu-Buet, D, Wagner-Ballon, O, Saada, V, et al. Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia. Blood. 2015;125:3618–26.Google Scholar
Orazi, A, Germing, U. The myelodysplastic/myeloproliferative neoplasms: myeloproliferative diseases with dysplastic features. Leukemia. 2008;22:1308–19.Google Scholar
Sangiorgio, VFI, Arber, DA, Orazi, A. How I investigate chronic myelomonocytic leukemia. Int J Lab Hematol. 2020 Apr;42(2):101–8. doi: 10.1111/ijlh.13145. Epub 2019 Dec 16. Review. PubMed PMID: 31841277.Google Scholar
Arber, DA, Orazi, A. Update on the pathologic diagnosis of chronic myelomonocytic leukemia. Mod Pathol. 2019 Jun;32(6):732–40. doi: 10.1038/s41379-019-0215-y. Epub 2019 Feb 5. Review. PubMed PMID: 30723295.Google Scholar
Kampalath, B, Cleveland, RP, Chang, CC, et al. Monocytes with altered phenotypes in posttrauma patients. Arch Pathol Lab Med. 2003;127:1580–5.CrossRefGoogle ScholarPubMed
Xu, Y, McKenna, RW, Karandikar, NJ, et al. Flow cytometric analysis of monocytes as a tool for distinguishing chronic myelomonocytic leukemia from reactive monocytosis. Am J Clin Pathol. 2005;124:799–806.Google Scholar
Caudill, JS, Sternberg, AJ, Li, CY, et al. C-terminal nucleophosmin mutations are uncommon in chronic myeloid disorders. Br J Haematol. 2006;133:638–41.Google Scholar
Oki, Y, Jelinek, J, Beran, M, et al. Mutations and promoter methylation status of NPM1 in myeloproliferative disorders. Haematologica. 2006;91:1147–8.Google Scholar
Ernst, T, Chase, A, Zoi, K, et al. Transcription factor mutations in myelodysplastic/myeloproliferative neoplasms. Haematologica. 2010;95:1473–80.Google Scholar
Itzykson, R, Kosmider, O, Renneville, A, et al. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol. 2013;31:2428–36.Google Scholar
Peng, J, Zuo, Z, Fu, B, et al. Chronic myelomonocytic leukemia with nucleophosmin (NPM1) mutation. Eur J Haematol. 2016;96:65–71.Google Scholar
Courville, EL, Wu, Y, Kourda, J, et al. Clinicopathologic analysis of acute myeloid leukemia arising from chronic myelomonocytic leukemia. Mod Pathol. 2013;26:751–61.Google Scholar
Schnittger, S, Bacher, U, Haferlach, C, et al. Characterization of NPM1-mutated AML with a history of myelodysplastic syndromes or myeloproliferative neoplasms. Leukemia. 2011;25:615–21.Google Scholar
Foucar, K, Hsi, ED, Wang, SA, et al. Concordance among hematopathologists in classifying blasts plus promonocytes: a bone marrow pathology group study. Int J Lab Hematol. 2020 Apr 16. doi: 10.1111.Google Scholar
Rose, D, Haferlach, T, Schnittger, S, et al. Subtype-specific patterns of molecular mutations in acute myeloid leukemia. Leukemia. 2016;31:11–17.Google Scholar
Shen, Y, Zhu, YM, Fan, X, et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood. 2011;118:5593–603.Google Scholar
Petrova-Drus, K, Chiu, A, Margolskee, E, et al. Bone marrow fibrosis in chronic myelomonocytic leukemia is associated with increased megakaryopoiesis, splenomegaly and with a shorter median time to disease progression. Oncotarget. 2017;8:103,274–82.Google Scholar
Khan, M, Muzzafar, T, Kantarjian, H, et al. Association of bone marrow fibrosis with inferior survival outcomes in chronic myelomonocytic leukemia. Ann Hematol. 2018;97:1183–91.Google Scholar
Gur, HD, Loghavi, S, Garcia-Manero, G, et al. Chronic myelomonocytic leukemia with fibrosis is a distinct disease subset with myeloproliferative features and frequent JAK2 p.V617F mutations. Am J Surg Pathol. 2018;42:799–806.Google Scholar
Chapman, J, Geyer, JT, Khanlari, M, et al. Myeloid neoplasms with features intermediate between primary myelofibrosis and chronic myelomonocytic leukemia. Mod Pathol. 2018;31:429–41.Google Scholar
Boiocchi, L, Espinal-Witter, R, Geyer, JT, et al. Development of monocytosis in patients with primary myelofibrosis indicates an accelerated phase of the disease. Mod Pathol. 2013;26:204–12.Google Scholar
Ricci, C, Fermo, E, Corti, S, et al. RAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant. Clin Cancer Res. 2010;16:2246–56.Google Scholar
Kohlmann, A, Grossmann, V, Klein, HU, 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.Google Scholar
Kosmider, O, Gelsi-Boyer, V, Ciudad, M, et al. TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia. Haematologica. 2009;94:1676–81.Google Scholar
Bacher, U, Haferlach, T, Schnittger, S, et al. Recent advances in diagnosis, molecular pathology and therapy of chronic myelomonocytic leukaemia. Br J Haematol. 2011;153:149–67.Google Scholar
Schuler, E, Schroeder, M, Neukirchen, J, et al. Refined medullary blast and white blood cell count based classification of chronic myelomonocytic leukemias. Leuk Res. 2014;38:1413–19.Google Scholar
Such, E, Germing, U, Malcovati, L, et al. Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia. Blood. 2013;121:3005–15.Google Scholar
Elena, C, Galli, A, Such, E, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood. 2016;128:1408–17.Google Scholar
Patnaik, MM, Padron, E, LaBorde, RR, et al. Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes. Leukemia. 2013;27:1504–10.Google Scholar
Kraemer, D, Rudiger, T, Reimer, P, et al. Splenectomy in patients with mixed myelodysplastic/myeloproliferative disease. Ann Hematol. 2002;81:308–11.CrossRefGoogle ScholarPubMed
Boiocchi, L, Gianelli, U, Iurlo, A, et al. Neutrophilic leukocytosis in advanced stage polycythemia vera: hematopathologic features and prognostic implications. Mod Pathol. 2015;28:1448–57.Google Scholar
Maxson, JE, Gotlib, J, Pollyea, DA, et al. Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. New Eng J Med. 2013;368:1781–90.Google Scholar
Pardanani, A, Lasho, TL, Laborde, RR, et al. CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia. 2013;27:1870–3.Google Scholar
Gotlib, J, Maxson, JE, George, TI, et al. The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment. Blood. 2013;122:1707–11.Google Scholar
Elliott, MA, Tefferi, A. Chronic neutrophilic leukemia: 2018 update on diagnosis, molecular genetics and management. Am J Hematol. 2018;93:578–87.Google Scholar
Papaemmanuil, E, Gerstung, M, Malcovati, L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122:3616–27; quiz 3699.Google Scholar
Haferlach, T, Nagata, Y, Grossmann, V, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014;28:241–7.Google Scholar
Shou, LH, Cao, D, Dong, XH, et al. Prognostic significance of SETBP1 mutations in myelodysplastic syndromes, chronic myelomonocytic leukemia, and chronic neutrophilic leukemia: a meta-analysis. PloS One. 2017;12:e0171608.Google Scholar
Safley, AM, Sebastian, S, Collins, TS, et al. Molecular and cytogenetic characterization of a novel translocation t(4;22) involving the breakpoint cluster region and platelet-derived growth factor receptor-alpha genes in a patient with atypical chronic myeloid leukemia. Gene Chromosome Canc. 2004;40:44–50.Google Scholar
Fend, F, Horn, T, Koch, I, et al. Atypical chronic myeloid leukemia as defined in the WHO classification is a JAK2 V617F negative neoplasm. Leuk Res. 2008;32:1931–5.Google Scholar
Piazza, R, Valletta, S, Winkelmann, N, et al. Recurrent SETBP1 mutations in atypical chronic myeloid leukemia. Nat Genet. 2013;45:18–24.Google Scholar
Gambacorti-Passerini, CB, Donadoni, C, Parmiani, A, et al. Recurrent ETNK1 mutations in atypical chronic myeloid leukemia. Blood. 2015;125:499–503.Google Scholar
Wang, SA, Hasserjian, RP, Fox, PS, et al. Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms. Blood. 2014;123:2645–51.Google Scholar
Elliott, MA, Tefferi, A. Chronic neutrophilic leukemia 2014: Update on diagnosis, molecular genetics, and management. Am J Hematol. 2014;89:651–8.Google Scholar
Kurzrock, R, Bueso-Ramos, CE, Kantarjian, H, et al. BCR rearrangement-negative chronic myelogenous leukemia revisited. J Clin Oncol. 2001;19:2915–26.Google Scholar
Breccia, M, Biondo, F, Latagliata, R, et al. Identification of risk factors in atypical chronic myeloid leukemia. Haematologica. 2006;91:1566–8.Google Scholar
Niemeyer, CM, Kang, MW, Shin, DH, et al. Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Nat Genet. 2010;42:794–800.CrossRefGoogle ScholarPubMed
Loh, ML. Recent advances in the pathogenesis and treatment of juvenile myelomonocytic leukaemia. Br J Haematol. 2011;152:677–87.Google Scholar
Rosser, A, Swallow, G, Swann, RA, et al. Salmonella enteritidis necrotising fasciitis in a multiple myeloma patient receiving bortezomib. Int J Hematol. 2010;91:149–51.Google Scholar
Niemeyer, CM, Arico, M, Basso, G, et al. Chronic myelomonocytic leukemia in childhood: a retrospective analysis of 110 cases. European Working Group on Myelodysplastic Syndromes in Childhood (EWOG-MDS). Blood. 1997;89:3534–43.Google Scholar
Matsumoto, K, Miki, J, Matsuzaki, S, et al. Skin infiltration of juvenile myelomonocytic leukemia. J Dermatol. 2004;31:748–51.Google Scholar
Gupta, RK, Qureshi, A, Choi, JK. Histologic findings in skin biopsy in a JMML rash: a case report and review of literature. Pediatr Devel Pathol. 2014;17:130–3.Google Scholar
Ng, CS, Lam, TK, Chan, JK, et al. Juvenile chronic myeloid leukemia. A malignancy of S-100 protein-positive histiocytes. Am J Clin Pathol. 1988;90:575–82.Google Scholar
Ozono, S, Inada, H, Nakagawa, S, et al. Juvenile myelomonocytic leukemia characterized by cutaneous lesion containing Langerhans cell histiocytosis-like cells. Int J Hematol. 2011;93:389–93.CrossRefGoogle ScholarPubMed
Niemeyer, CM, Kratz, CP. Paediatric myelodysplastic syndromes and juvenile myelomonocytic leukaemia: molecular classification and treatment options. Br J Haematol. 2008;140:610–24.Google Scholar
Luna-Fineman, S, Shannon, KM, Atwater, SK, et al. Myelodysplastic and myeloproliferative disorders of childhood: a study of 167 patients. Blood. 1999;93:459–66.Google Scholar
Locatelli, F, Niemeyer, CM. How I treat juvenile myelomonocytic leukemia. Blood. 2015;125:1083–90.Google Scholar
Sakashita, K, Matsuda, K, Koike, K. Diagnosis and treatment of juvenile myelomonocytic leukemia. Pediatr Int. 2016;58:681–90.CrossRefGoogle ScholarPubMed
Honda, Y, Tsuchida, M, Zaike, Y, et al. Clinical characteristics of 15 children with juvenile myelomonocytic leukaemia who developed blast crisis: MDS Committee of Japanese Society of Paediatric Haematology/Oncology. Br J Haematol. 2014;165:682–7.Google Scholar
Niemeyer, CM, Kang, MW, Shin, DH, et al. Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Nat Genet. 2010;42:794–800.Google Scholar
Muraoka, M, Okuma, C, Kanamitsu, K, et al. Adults with germline CBL mutation complicated with juvenile myelomonocytic leukemia at infancy. J Hum Genet. 2016;61:523–6.Google Scholar
Pathak, A, Pemov, A, McMaster, ML, et al. Juvenile myelomonocytic leukemia due to a germline CBL Y371C mutation: 35-year follow-up of a large family. Hum Genet. 2015;134:775–87.Google Scholar
Schmitt-Graeff, A, Thiele, J, Zuk, I, et al. Essential thrombocythemia with ringed sideroblasts: a heterogeneous spectrum of diseases, but not a distinct entity. Haematologica. 2002;87:392–9.Google Scholar
Raya, JM, Arenillas, L, Domingo, A, et al. Refractory anemia with ringed sideroblasts associated with thrombocytosis: comparative analysis of marked with non-marked thrombocytosis, and relationship with JAK2 V617F mutational status. Int J Hematol. 2008;88:387–95.Google Scholar
Malcovati, L, Della Porta, MG, Pietra, D, et al. Molecular and clinical features of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Blood. 2009;114:3538–45.Google Scholar
Schmitt-Graeff, AH, Teo, SS, Olschewski, M, et al. JAK2V617F mutation status identifies subtypes of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Haematologica. 2008;93:34–40.Google Scholar
Malcovati, L, Papaemmanuil, E, Bowen, DT, et al. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood. 2011;118:6239–46.Google Scholar
Patnaik, MM, Lasho, TL, Finke, CM, et al. Predictors of survival in refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) and the role of next-generation sequencing. Am J Hematol. 2016;91:492–8.Google Scholar
Wang, SA, Hasserjian, RP, Loew, JM, et al. Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features. Leukemia. 2006;20:1641–4.Google Scholar
Atallah, E, Nussenzveig, R, Yin, CC, et al. Prognostic interaction between thrombocytosis and JAK2 V617F mutation in the WHO subcategories of myelodysplastic/myeloproliferative disease-unclassifiable and refractory anemia with ringed sideroblasts and marked thrombocytosis. Leukemia. 2008;22:1295–8.Google Scholar
Cannella, L, Breccia, M, Latagliata, R, et al. Clinical and prognostic features of patients with myelodysplastic/myeloproliferative syndrome categorized as unclassified (MDS/MPD-U) by WHO classification. Leuk Res. 2008;32:514–16.Google Scholar
Broseus, J, Florensa, L, Zipperer, E, et al. Clinical features and course of refractory anemia with ring sideroblasts associated with marked thrombocytosis. Haematologica. 2012;97:1036–41.CrossRefGoogle ScholarPubMed
Wang, SA, Galili, N, Cerny, J, et al. Chronic myelomonocytic leukemia evolving from preexisting myelodysplasia shares many features with de novo disease. Am J Clin Pathol. 2006;126:789–97.Google Scholar
Sakaguchi, H, Okuno, Y, Muramatsu, H, et al. Exome sequencing identifies secondary mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia. Nat Genet. 2013;45:937–41.Google Scholar
Perez, B, Kosmider, O, Cassinat, B, et al. Genetic typing of CBL, ASXL1, RUNX1, TET2 and JAK2 in juvenile myelomonocytic leukaemia reveals a genetic profile distinct from chronic myelomonocytic leukaemia. Br J Haematol. 2010;151:460–8.Google Scholar
Sugimoto, Y, Muramatsu, H, Makishima, H, et al. Spectrum of molecular defects in juvenile myelomonocytic leukaemia includes ASXL1 mutations. Br J Haematol. 2010;150:83–7.Google Scholar
Stieglitz, E, Troup, CB, Gelston, LC, et al. Subclonal mutations in SETBP1 confer a poor prognosis in juvenile myelomonocytic leukemia. Blood. 2015;125:516–24.Google Scholar

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