RAS Mutation Is a Poor Prognostic Factor in Patients with Chronic Myelomonocytic Leukemia
Liping Zhang, Tariq N Aladily, Zaher Chakhachiro, Hui Yao, Xiaoping Su, Mark Routbort, Sa A Wang, Raja Luthra, Roberto Miranda, L Jeffrey Medeiros, Carlos Bueso-Ramos, Joseph D Khoury. MD Anderson Cancer Center, Houston, TX
Background: Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative neoplasm without known consistent genetic abnormalities. Although KRAS and NRAS mutations are identified in sizeable subsets of CMML cases and can serve as an ancillary diagnostic tool, the clinicopathologic associations and prognostic implications of RAS mutations remain poorly characterized.
Design: We conducted a retrospective analysis of molecular diagnostic results and clinicopathologic features of patients diagnosed with CMML between 2003 and 2012. Study inclusion criteria included availability of RAS mutation results and survival data. RAS mutations were assessed using PCR-based DNA sequencing of codons 12, 13 and 61 of the KRAS and NRAS genes.
Results: The study group included 81 patients with CMML. There were 54 men and 27 women with a median age at diagnosis of 67 years (range, 27 to 84 years). The median clinical follow up was 21.5 months (range, 0 to 94.2 months). Forty-five (56%) patients in this study group had RAS mutation; 24 with KRAS mutation, 19 with NRAS mutation, and 2 with both KRAS and NRAS mutations. Overall survival was lower and incidence of death was higher in patients with RAS mutation than in patients without RAS mutation (p=0.03, logrank test; p=0.00037, Fisher's exact test). A trend suggestive of worse overall survival among patients with KRAS mutation compared to those with NRAS mutation was noted (p=0.09, logrank test). Multivariate analysis suggested that RAS mutation status is independently associated with clinical outcome after adjusting for bone marrow and peripheral blood blast counts as well as the results of conventional cytogenetic risk groups stratified according to the Revised International Prognostic Scoring System (p=0.05, Cox proportional-Hazards regression).
Conclusions: These findings suggest that KRAS and/or NRAS mutations can serve as prognostic markers in CMML patients and portend a more adverse clinical outcome.
Tuesday, March 5, 2013 11:00 AM
Proffered Papers: Section C, Tuesday Morning