Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival

• Published in: Leukemia Vol. 22; no. 4; pp. 756 - 761
• Main Authors: TEFFERI, A, LASHOL, T. L, HUANG, J, FINKE, C, MESA, R. A, LI, C. Y, WU, W, HANSON, C. A, PARDANANI, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.04.2008; Nature Publishing Group
• Subjects: Adult; Age Factors; Aged; Aged, 80 and over; Alleles; Biological and medical sciences; Blood platelets; Bone marrow; Bone Marrow Examination; Care and treatment; Deoxyribonucleic acid; Disease-Free Survival; DNA; Female; Gene Frequency; Gene mutations; Genetic aspects; Health aspects; Hematologic and hematopoietic diseases; Hematology; Hemoglobin; Humans; Janus Kinase 2 - genetics; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukocytes; Male; Medical prognosis; Medical sciences; Middle Aged; Mutants; Mutation; Mutation, Missense; Myelofibrosis; Patients; Peripheral blood; Phenotypes; Platelet Count; Polymerase chain reaction; Primary Myelofibrosis - epidemiology; Primary Myelofibrosis - genetics; Primary Myelofibrosis - mortality; Pruritus; Qualitative analysis; Quartiles; Spleen; Survival; Survival Rate; Thromboembolism; Thrombosis; United States; United States > US; Prognosis; Myelofibrosis; Hematology; Enzyme; JAK2 protein tyrosine kinase; Transferases; Leukemia; Malignant hemopathy; Survival; Myeloproliferative syndrome; Allele; V617F; Genetics; JAK2W7F; JAK2; Protein-tyrosine kinase; Comparative study; Cancer
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2405097

The clinical relevance of JAK2V617F allele burden in primary myelofibrosis (PMF) has not been previously studied. Bone marrow-derived DNA from 199 patients with PMF was subjected to qualitative (n=199) and quantitative (n=129) analysis for V617F. Mutational frequency was 58% and median mutant allele burden ratio in V617F-positive patients was 29% (range, 1-74%). Multivariable analysis identified older age, platelet count > or =100 x 10(9) l(-1) and peripheral blood blast percentage <3% as being associated with a positive mutational status. The mere presence of the mutation did not affect the incidence of thrombosis (P=0.78), overall survival (P=0.22) or leukemia-free survival (P=0.5). The 129 patients with allele burden information were divided into four groups: V617F-negative (n=53) and V617F-positive with mutant allele burden in the lower quartile (n=19), middle quartiles (n=38) or upper quartile (n=19) range. Kaplan-Meier plots revealed significantly shortened overall (P=0.0008) and leukemia-free (P=0.01) survival for the lower quartile, but not for upper quartile allele burden group; independent prognostic relevance was validated by multivariable analysis. We conclude that low V617F allele burden in PMF might indicate the presence of an overriding V617F-negative clone that confers a more aggressive disease phenotype.