Use of CBL exon 8 and 9 mutations in diagnosis of myeloproliferative neoplasms and myelodysplastic/myeloproliferative disorders: an analysis of 636 cases

• Published in: Haematologica (Roma) Vol. 97; no. 12; pp. 1890 - 1894
• Main Authors: SCHNITTGER, Susanne, BACHER, Ulrike, KERN, Wolfgang, HAFERLACH, Claudia, HAFERLACH, Torsten, ALPERMANN, Tamara, REITER, Andreas, ULKE, Madlen, DICKER, Frank, EDER, Christiane, KOHLMANN, Alexander, GROSSMANN, Vera, KOWARSCH, Andreas
• Format: Journal Article
• Language: English
• Published: Pavia Ferrata Storti Foundation 01.12.2012
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Amino Acid Sequence; Biological and medical sciences; Chronic Myeloproliferative Disorders; Cohort Studies; Female; Follow-Up Studies; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Mutation - genetics; Myeloproliferative Disorders - genetics; Prognosis; Proto-Oncogene Proteins c-cbl - genetics; Young Adult; myeloproliferative neoplasms; Prognosis; Hematology; Exon 8; Malignant hemopathy; Adaptor protein; Myelodysplastic syndrome; Myeloproliferative syndrome; CBL mutations; Chronic myelomonocytic leukemia; Genetics; Diagnosis; Mutation; Sequencing; Cancer
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2012.065375

We analyzed 636 patients with diverse myeloproliferative neoplasms or myelodysplastic/myeloproliferative neoplasms for mutations of the Casitas B-cell lymphoma gene (CBL(mut)) in exons 8 and 9 and performed correlations to other genetic alterations. CBL(mut) were detected in 63 of 636 (9.9%) of these selected patients. CBL(mut) were more frequent in myelodysplastic/myeloproliferative neoplasms than myeloproliferative neoplasms (51 of 328, 15.5% vs. 12 of 291, 4.1%; P<0.001). Frequency was 48 of 278 (17.3%) in chronic myelomonocytic leukemia and 3 of 33 (9.1%) in unclassifiable myelodysplastic/myeloproliferative neoplasms. CBL(mut) was not detected in polycythemia vera, primary myelofibrosis, essential thrombocythemia, or refractory anemia with ring sideroblasts and marked thrombocytosis. CBL(mut) were underrepresented in JAK2(V617F) mutated as compared to JAK2V617(wt) cases (P<0.001), and mutually exclusive of JAK2exon12(mut) and MPLW515(mut). CBL(mut) were associated with monosomy 7 (P=0.008) and TET2(mut) (P=0.003). In chronic myelomonocytic leukemia, CBL(mut) had no significant impact on survival outcomes. Therefore, CBL(mut) are frequent in chronic myelomonocytic leukemia, absent in classical myeloproliferative neoplasms, and are only exceptionally found in coincidence with JAK-STAT pathway activating mutations.