title: Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: a Mayo Clinic-French Consortium Study.
abstract: Four hundred and nine patients with chronic myelomonocytic leukemia (CMML) were included in the international collaborative study (268 (66%) and 141 (34%) from Mayo clinic and French consortium respectively). Thirty percent displayed an abnormal karyotype, including; 72% sole, 16% two, and 11% complex abnormalities. The most common abnormalities included; +8 (23%), -Y (20%), -7/7q-(14%), 20q- (8%), +21 (8%), and der(3q) (8%). Patients with an abnormal karyotype were more likely to be elderly (P = 0.03), be anemic (P = 0.0009), have leukocytosis (P = 0.02) with neutrophilia (P = 0.03), demonstrate increased circulating immature myeloid cells (P = 0.0003), peripheral blood blasts (P < 0.0001), and bone marrow blasts (P < 0.0001). ASXL1 (P = 0.04) and SF3B1 (P = 0.03) mutations clustered with an abnormal karyotype, whereas SRSF2 (P = 0.02) mutations occurred more commonly with a normal karyotype. A step-wise survival analysis resulted in three distinct cytogenetic risk categories: high (complex and monosomal karyotypes), intermediate (all abnormalities not in the high or low risk groups) and low [normal, sole -Y and sole der (3q)] with median survivals of 3 [hazard ratio (HR) = 8.1, 95% confidence interval (CI) = 4.6-14.2], 20 (HR = 1.7, 95% CI = 1.2-2.3) and 41 months, respectively. In multivariable analysis, this particular cytogenetic risk stratification remained significant in the context of the Molecular Mayo Model (P < 0.0001), MD Anderson prognostic model (P < 0.0001), the GFM CMML model (P < 0.0001) and was effective in predicting leukemic transformation (P = 0.004).
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN.
authors.forename: Emnet A
authors.initials: EA
authors.lastname: Wassie
authors.forename: Raphael
authors.initials: R
authors.lastname: Itzykson
authors.forename: Terra L
authors.initials: TL
authors.lastname: Lasho
authors.forename: Olivier
authors.initials: O
authors.lastname: Kosmider
authors.forename: Christy M
authors.initials: CM
authors.lastname: Finke
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.forename: Rhett P
authors.initials: RP
authors.lastname: Ketterling
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
authors.forename: Mrinal M
authors.initials: MM
authors.lastname: Patnaik
mesh_terms: D059786:Abnormal Karyotype; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007391:International Cooperation; D015477:Leukemia, Myelomonocytic, Chronic / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D007964:Leukocytosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011379:Prognosis; D000072260:RNA Splicing Factors; D012097:Repressor Proteins / Q000235:genetics; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics; D012306:Risk; D000068103:Serine-Arginine Splicing Factors; D016019:Survival Analysis
chemical_list: C473949:ASXL1 protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D012097:Repressor Proteins; D017413:Ribonucleoprotein, U2 Small Nuclear; D012261:Ribonucleoproteins; C112491:SF3B1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors