title: Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms.
abstract: Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) largely defined morphologically. It is, unclear, however, whether aCML-associated features are distinctive enough to allow its separation from unclassifiable MDS/MPN (MDS/MPN-U). To study these 2 rare entities, 134 patient archives were collected from 7 large medical centers, of which 65 (49%) cases were further classified as aCML and the remaining 69 (51%) as MDS/MPN-U. Distinctively, aCML was associated with many adverse features and an inferior overall survival (12.4 vs 21.8 months, P = .004) and AML-free survival (11.2 vs 18.9 months, P = .003). The aCML defining features of leukocytosis and circulating myeloid precursors, but not dysgranulopoiesis, were independent negative predictors. Other factors, such as lactate dehydrogenase, circulating myeloblasts, platelets, and cytogenetics could further stratify MDS/MPN-U but not aCML patient risks. aCML appeared to have more mutated RAS (7/20 [35%] vs 4/29 [14%]) and less JAK2p.V617F (3/42 [7%] vs 10/52 [19%]), but was not statistically significant. Somatic CSF3R T618I (0/54) and CALR (0/30) mutations were not detected either in aCML or MDS/MPN-U. In conclusion, within MDS/MPN, the World Health Organization 2008 criteria for aCML identify a subgroup of patients with features clearly distinct from MDS/MPN-U. The MDS/MPN-U category is heterogeneous, and patient risk can be further stratified by a number of clinicopathological parameters.
authors.affiliation: Department of Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX;
authors.forename: Sa A
authors.initials: SA
authors.lastname: Wang
authors.forename: Robert P
authors.initials: RP
authors.lastname: Hasserjian
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Fox
authors.forename: Heesun J
authors.initials: HJ
authors.lastname: Rogers
authors.forename: Julia T
authors.initials: JT
authors.lastname: Geyer
authors.forename: Devon
authors.initials: D
authors.lastname: Chabot-Richards
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Weinzierl
authors.forename: Joseph
authors.initials: J
authors.lastname: Hatem
authors.forename: Jesse
authors.initials: J
authors.lastname: Jaso
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kanagal-Shamanna
authors.forename: Francesco C
authors.initials: FC
authors.lastname: Stingo
authors.forename: Keyur P
authors.initials: KP
authors.lastname: Patel
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Mehrotra
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.forename: Courtney D
authors.initials: CD
authors.lastname: Dinardo
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Ramon V
authors.initials: RV
authors.lastname: Tiu
authors.forename: Adam
authors.initials: A
authors.lastname: Bagg
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Arber
authors.forename: Kathryn
authors.initials: K
authors.lastname: Foucar
authors.forename: Raja
authors.initials: R
authors.lastname: Luthra
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D042381:Granulocyte Precursor Cells / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000145:classification / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007621:Karyotyping; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000175:diagnosis* / Q000235:genetics; D007964:Leukocytosis / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis* / Q000235:genetics; D054437:Myelodysplastic-Myeloproliferative Diseases / Q000175:diagnosis* / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D007770:L-Lactate Dehydrogenase