Please use this identifier to cite or link to this item: http://nopr.niscair.res.in/handle/123456789/29085
Title: NRAS Mutations in de novo acute leukemia: Prevalence and clinical significance
Authors: Dunna, Nageswara Rao
Vuree, Sugunakar
Anuradha, Cingeetham
Sailaja, Kagita
Surekha, Damineni
Digumarti, Raghunadha Rao
Rao, V R
Yadav, Satish Kumar
Reddy, Rajasekhar
Vishnupriya, Satti
Keywords: NRAS mutations;Acute lymphoblastic leukemia;Acute myeloid leukemia;GTPase;Hematopoietic malignancies
Issue Date: Jun-2014
Publisher: NISCAIR-CSIR, India
Abstract: The activating mutations of the Ras gene or other abnormalities in Ras signaling pathway lead to uncontrolled growth factor-independent proliferation of hematopoietic progenitors. Oncogenic mutations in NRAS gene have been observed with variable prevalence in hematopoietic malignancies. In the present study, NRAS mutations were detected using bidirectional sequencing in 264 acute leukemia cases — 129 acute lymphocytic leukemia (ALL) and 135 acute myeloid leukemia (AML) and 245 age- and gender-matched controls. Missense mutation was observed only in the 12th codon of NRAS gene in 4.7% of AML and 3.16% of ALL cases. The presence of NRAS mutation did not significantly influence blast % and lactate dehydrogenase (LDH) levels in AML patients. When the data were analyzed with respect to clinical variables, the total leukocyte count was elevated for mutation positive group, compared to negative group. In AML patients with NRAS mutations, 60% failed to achieve complete remission (CR), as compared to 34.8% in mutation negative group. These results indicated that NRAS mutations might confer poor drug response. In AML, disease free survival (DFS) in NRAS mutation positive group was lesser, compared to mutation negative group (9.5 months vs. 11.68 months). In ALL patients, DFS of NRAS mutation positive group was lesser than mutation negative group (9.2 months vs. 27.5 months). The CR rate was also lower for mutation-positive patients group, compared to mutation-negative group. In conclusion, these results suggested that presence of NRAS mutation at 12th codon was associated with poor response and poorer DFS in both ALL and AML.
Page(s): 207-210
URI: http://hdl.handle.net/123456789/29085
ISSN: 0975-0959 (Online); 0301-1208 (Print)
Appears in Collections:IJBB Vol.51(3) [June 2014]

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