Classifying Chronic Myelomonocytic Leukemia
Authors: L. L. Yavorkovsky, P. Cook, Peter Greenberg, Jeanne Anderson, Eli Estey, Pierre Fenaux, Terry Hamblin, Eva Hellstrom-Lindberg, Alan List, Kazuma Ohyashiki, Guillermo Sanz, Miguel Sanz
Journal: Journal of Clinical Oncology (2001)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.17.3790 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11533106 Classifying Chronic Myelomonocytic Leukemia L. L. YavorkovskyxL. L. YavorkovskySearch for articles by this author , P. CookxP. CookSearch for articles by this author Peter GreenbergxPeter GreenbergSearch for articles by this author , Jeanne AndersonxJeanne AndersonSearch for articles by this author , Eli Estey, M.D.xEli EsteySearch for articles by this author , Pierre FenauxxPierre FenauxSearch for articles by this author , Terry HamblinxTerry HamblinSearch for articles by this author , Eva Hellstrom-LindbergxEva Hellstrom-LindbergSearch for articles by this author , Alan ListxAlan ListSearch for articles by this author , Kazuma OhyashikixKazuma OhyashikiSearch for articles by this author , Guillermo SanzxGuillermo SanzSearch for articles by this author , Miguel SanzxMiguel SanzSearch for articles by this author , For the International MDS Study GroupxSearch for articles by this author Show More The Brooklyn Hospital Center, Brooklyn, NY, New York University Medical Center, New York, NYStanford University Medical Center, Stanford, CAUniversity of Texas Health Sciences Center, San Antonio, TX Anderson Cancer Center, Houston, TXServices des Maladies du San, Lille, FranceRoyal Bournemouth Hospital, Bournemouth, United KingdomKarolinska Institute, Huddinge, SwedenUniversity of Arizona Cancer Center, Tucson, AZTokyo Medical University, Tokyo, JapanHospital Universitario La Fe, Valencia, Spain https://doi.org/10.1200/JCO.2001.19.17.3790 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse01092001In Reply:Drs Yavorkovsky and Cook comment on difficulties inherent in the term “chronic myelomonocytic leukemia” (CMML), one of the issues we raised in our discussion of concerns1 about the recent proposals by the World Health Organization’s panel for reclassifying myelodysplastic syndromes (MDSs).2 Although CMML was initially included within the MDSs by the French-American-British group,3 its clinical and biologic heterogeneity is well recognized. The proliferative form of CMML (ie, with high WBC counts, hepatosplenomegaly, and constitutional symptoms) is more characteristic of a myeloproliferative disorder (MPD) that of an MDS.4-8 The disorder differs in its management issues (ie, control of hyperleukocytosis, organomegaly, and their consequences) and major clinical features from the nonproliferative subtype of CMML (ie, MDS accompanied by monocytosis but relatively low WBC counts); patients with the latter subtype previously were likely considered to have monocystosis as a component of their refractory anemia or refractory anemia with excess blasts. Clinical outcomes in CMML are more closely related to their proportion of marrow blasts than to their peripheral monocyte numbers.5,6,9For these reasons, the International MDS Risk Analysis Workshop (IMRAW)10 and others7 attempted to diminish the heterogeneity present within MDS by excluding from this entity the proliferative type of CMML, including only those with WBC counts less than 12,000/mm3. Although the recent World Health Organization panel initially placed all CMML patients in a separate category (MDS/MPD),2 this proposal has subsequently been revised such that the same leukocyte count as used by the Workshop was utilized to separate MDS from MDS/MPD (the latter including proliferative CMML).11 Despite this segregation, we agree with Yavorkovsky and Cook that clinical heterogeneity remains; some MDS patients with monocytosis and dysplasia may develop a proliferative phase akin to CMML.Biologic as well as clinical features also segregate the two types of CMML. Molecular lesions that result in a “gain of function,” including activating ras and c-fms oncogene mutations, which are capable of altering cell proliferation patterns, are common features of hemopoietic cells in proliferative-type CMML and in patients with undifferentiated MPD, but less so for MDS.12-14 In addition, cytogenetic changes, such as the t(5;12) translocation, which results in a fusion protein between the platelet-derived growth factor receptor beta and the transcription factor tel, are present in a subset of CMML patients.15 Related to these findings, biologic features of hemopoietic precursors from juvenile myelomonocytic leukemia (a disease similar to proliferative CMML) demonstrate in vitro hyperresponsiveness to myeloid growth factors arising from inactivating mutations of the GTPase, NF1, and unrestrained ras activation.16,17Thus, important focus is needed to extend the debate regarding these patients. 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