ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients

• Published in: Leukemia Vol. 28; no. 11; pp. 2206 - 2212
• Main Authors: Patnaik, M M, Itzykson, R, Lasho, T L, Kosmider, O, Finke, C M, Hanson, C A, Knudson, R A, Ketterling, R P, Tefferi, A, Solary, E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-11-2014; Nature Publishing Group
• Subjects: 45; 45/23; 631/67/68; Adult; Aged; Aged, 80 and over; Blood tests; Cancer Research; Carrier Proteins - genetics; Chronic myelomonocytic leukemia; Codon, Nonsense; Confidence intervals; Consortia; Critical Care Medicine; Female; Frameshift Mutation; Genetic aspects; Genetic Testing; Hematology; Hematopoietic stem cells; Hemoglobin; Humans; Intensive; Internal Medicine; Leukemia; Leukemia research; Leukemia, Myelomonocytic, Chronic - genetics; Leukemia, Myelomonocytic, Chronic - mortality; Male; Medicine; Medicine & Public Health; Middle Aged; Models, Statistical; Monocytes; Multivariate Analysis; Mutation; Mutation (Biology); Myeloid cells; Myelomonocytic leukemia; Nuclear Proteins - genetics; Oncology; original-article; Physiological aspects; Platelets; Prognosis; Regression coefficients; Regression models; Repressor Proteins - genetics; Risk analysis; Risk Factors; Statistical analysis; Survival; Survival Analysis; Young Adult; France; United States > US; Paris France
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2014.125

In a cohort of 466 patients, we sought to clarify the prognostic relevance of
ASXL1
and
SETBP1
mutations, among others, in World Health Organization-defined chronic myelomonocytic leukemia (CMML) and its added value to the Mayo prognostic model. In univariate analysis, survival was adversely affected by
ASXL1
(nonsense and frameshift) but not
SETBP1
mutations. In multivariable analysis,
ASXL1
mutations, absolute monocyte count >10 × 10(9)/l, hemoglobin <10 g/dl, platelets <100 × 10(9)/l and circulating immature myeloid cells were independently predictive of shortened survival: hazard ratio (95% confidence interval (CI)) values were 1.5 (1.1–2.0), 2.2 (1.6–3.1), 2.0 (1.6–2.6), 1.5 (1.2–1.9) and 2.0 (1.4–2.7), respectively. A regression coefficient-based prognostic model based on these five risk factors delineated high (≥3 risk factors; HR 6.2, 95% CI 3.7–10.4) intermediate-2 (2 risk factors; HR 3.4, 95% CI 2.0–5.6) intermediate-1 (one risk factor; HR 1.9, 95% CI 1.1–3.3) and low (no risk factors) risk categories with median survivals of 16, 31, 59 and 97 months, respectively. Neither
ASXL1
nor
SETBP1
mutations predicted leukemic transformation. The current study confirms the independent prognostic value of nonsense/frameshift
ASXL1
mutations in CMML and signifies its added value to the Mayo prognostic model, as had been shown previously in the French consortium model.