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RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years

RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years
RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years
The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. The RAS pathway has been implicated as a key component of the proliferative drive in AML. We have screened AML patients, predominantly younger than 60 years and treated within 2 clinical trials, for NRAS (n = 1106), KRAS (n = 739), and HRAS (n = 200) hot-spot mutations using denaturing high-performance liquid chromatography or restriction fragment length polymorphism (RFLP) analysis. NRAS mutations were confirmed in 11% of patients (126/1106) and KRAS mutations in 5% (39/739). No HRAS mutations were detected in 200 randomly selected samples. Codons most frequently mutated were N12 (43%), N13 (21%), and K12 (21%). KRAS mutations were relatively overrepresented in French-American-British (FAB) type M4 (P < .001). NRAS mutation was over-represented in the t(3;5)(q2125;q31q35) subgroup (P < .001) and underrepresented in t(15;17)(q22;q21) (P < .001). KRAS mutation was overrepresented in inv(16)(p13q22) (P = .004). Twenty-three percent of KRAS mutations were within the inv(16) subgroup. RAS mutation and FLT3 ITD were rarely coexistent (14/768; P < .001). Median percentage of RAS mutant allele assayed by quantitative RFLP analysis was 28% (N12), 19% (N13), 25% (N61), and 21% (K12). RAS mutation did not influence clinical outcome (overall/disease-free survival, complete remission, relapse rate) either for the entire cohort or within cytogenetic risk groups.
0006-4971
2113-2119
Bowen, D.T.
676c2629-037d-4ca2-ab7d-93a020a8a3d5
Frew, M.E.
0960ac6c-626b-4012-ab06-3a1ae0768385
Hills, R.
7c8318be-4842-45dd-9141-6b6e75b2b1e9
Gale, R.E.
d9ef9596-834d-4970-83b5-9f5718c163af
Wheatley, K.
ff351180-4419-4585-8bcb-81baff49bfa8
Groves, M.J.
05ad9ed8-a85d-4efa-9556-33fd6c040385
Langabeer, S.E.
6f818827-a1dd-4a9d-9c7d-2673d27ea163
Kottaridis, P.D.
f51b4efe-1483-4bcc-9c65-d53db32f2e76
Moorman, A.V.
af5027f3-4927-4e62-b1be-ac4bdcf6cd8f
Burnett, A.K.
a46b0e52-549d-4388-972a-d5a82e6a20fc
Linch, D.C.
f0834032-de86-48b7-a074-e0de94372aca
Bowen, D.T.
676c2629-037d-4ca2-ab7d-93a020a8a3d5
Frew, M.E.
0960ac6c-626b-4012-ab06-3a1ae0768385
Hills, R.
7c8318be-4842-45dd-9141-6b6e75b2b1e9
Gale, R.E.
d9ef9596-834d-4970-83b5-9f5718c163af
Wheatley, K.
ff351180-4419-4585-8bcb-81baff49bfa8
Groves, M.J.
05ad9ed8-a85d-4efa-9556-33fd6c040385
Langabeer, S.E.
6f818827-a1dd-4a9d-9c7d-2673d27ea163
Kottaridis, P.D.
f51b4efe-1483-4bcc-9c65-d53db32f2e76
Moorman, A.V.
af5027f3-4927-4e62-b1be-ac4bdcf6cd8f
Burnett, A.K.
a46b0e52-549d-4388-972a-d5a82e6a20fc
Linch, D.C.
f0834032-de86-48b7-a074-e0de94372aca

Bowen, D.T., Frew, M.E., Hills, R., Gale, R.E., Wheatley, K., Groves, M.J., Langabeer, S.E., Kottaridis, P.D., Moorman, A.V., Burnett, A.K. and Linch, D.C. (2005) RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic subgroups but does not influence outcome in patients younger than 60 years. Blood, 106 (6), 2113-2119. (doi:10.1182/blood-2005-03-0867).

Record type: Article

Abstract

The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of mutations promoting proliferation/survival and those impairing differentiation. The RAS pathway has been implicated as a key component of the proliferative drive in AML. We have screened AML patients, predominantly younger than 60 years and treated within 2 clinical trials, for NRAS (n = 1106), KRAS (n = 739), and HRAS (n = 200) hot-spot mutations using denaturing high-performance liquid chromatography or restriction fragment length polymorphism (RFLP) analysis. NRAS mutations were confirmed in 11% of patients (126/1106) and KRAS mutations in 5% (39/739). No HRAS mutations were detected in 200 randomly selected samples. Codons most frequently mutated were N12 (43%), N13 (21%), and K12 (21%). KRAS mutations were relatively overrepresented in French-American-British (FAB) type M4 (P < .001). NRAS mutation was over-represented in the t(3;5)(q2125;q31q35) subgroup (P < .001) and underrepresented in t(15;17)(q22;q21) (P < .001). KRAS mutation was overrepresented in inv(16)(p13q22) (P = .004). Twenty-three percent of KRAS mutations were within the inv(16) subgroup. RAS mutation and FLT3 ITD were rarely coexistent (14/768; P < .001). Median percentage of RAS mutant allele assayed by quantitative RFLP analysis was 28% (N12), 19% (N13), 25% (N61), and 21% (K12). RAS mutation did not influence clinical outcome (overall/disease-free survival, complete remission, relapse rate) either for the entire cohort or within cytogenetic risk groups.

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Published date: 2005

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Local EPrints ID: 26223
URI: http://eprints.soton.ac.uk/id/eprint/26223
ISSN: 0006-4971
PURE UUID: ee34da37-a278-40cf-b042-8c2f9f4fb217

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Date deposited: 20 Apr 2006
Last modified: 15 Jul 2019 19:14

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Contributors

Author: D.T. Bowen
Author: M.E. Frew
Author: R. Hills
Author: R.E. Gale
Author: K. Wheatley
Author: M.J. Groves
Author: S.E. Langabeer
Author: P.D. Kottaridis
Author: A.V. Moorman
Author: A.K. Burnett
Author: D.C. Linch

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