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Cited by 215Multiple Myeloma Research and TreatmentsChronic Lymphocytic Leukemia ResearchAcute Myeloid Leukemia Research

The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.

Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: analysis of the Eastern Cooperative Oncology Group Phase III Trial

Liu, P, Leong, T, Quam, L, Billadeau, D, Kay, NE, Greipp, P, Kyle, RA, Oken, MM, Van Ness, B·1996·Blood
DOI 10.1182/blood.v88.7.2699.bloodjournal8872699
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Abstract

Mutations of members of the ras family are among the most common oncogene mutations found in multiple myeloma (MM). We have examined the mutational status of the N- and K-ras genes at codons 12, 13, and 61 in 160 newly diagnosed MM patients enrolled on the Eastern Cooperative Oncology Group (ECOG) phase III clinical trial E9486. The total incidence of ras mutations was found to be 39% of the samples analyzed. Five patients showed evidence of more than one mutation. We obtained 22 marrow samples from patients at the time of disease progression or relapse, for whom a ras mutation was identified at diagnosis. In all cases, the ras mutation of the disease progression sample was identical to that found at diagnosis. In contrast, three of 25 patients who did not show any ras mutation at diagnosis acquired a ras mutation at the time of disease progression. No significant association was observed between any ras mutation and stage of disease, beta 2-microglobulin levels, labelling index, or protein type. The mean tumor burden and median survival for patients with mutations of N-ras was indistinguishable from patients with no ras mutations. However, patients with K-ras mutations had a significantly higher mean bone marrow tumor burden at diagnosis than patients with no ras mutations (57% v 36%, P ‼ .02); and the median survival of patients with a K-ras mutation was significantly shorter (2.0 v 3.7 years, P ‼ .02). To determine if the status of ras mutations could affect treatment response, we examined patient survival on the three treatment arms of E9486. Although the presence of a ras mutation in the multidrug treatment, VBMCP alone, showed a marginal significance, neither the VBMCP, nor the addition of interferon-alpha showed statistically significant survival differences between mutant and wildtype ras status. Interestingly, there appeared to be a statistically significant difference in survival of patients treated with VBMCP and alternating high doses of cyclophosphamide + prednisone. Patients with ras mutations had a median survival of 2.1 years; patients with wild-type ras had a median survival of 4.0 years (P ‼ .01).

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Crossref · 10.1182/blood.v88.7.2699.bloodjournal8872699

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Metadata

Authors
Liu, P., Leong, T., Quam, L., Billadeau, D., Kay, N., Greipp, P., Kyle, R., Oken, M., & Van Ness, B.
Affiliations
  • University of Minnesota (US)
  • University of Minnesota, Minneapolis, USA.
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
1996-10-01
Volume
88
Issue
7
Pages
2699-2706
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v88.7.2699.bloodjournal8872699
OpenAlex
W2294883787
Cited by
215
References
37
Citations by year
2025: 1 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 7 · 2018: 4 · 2017: 3 · 2016: 8 · 2015: 7 · 2014: 6 · 2013: 7 · 2012: 15
FWCI
3.03
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (CA32218, CA 15947, CA19853)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
Keywords
multiple myeloma, NRAS mutation, KRAS mutation, oncogenic Ras, codon 12 and 13 mutations, disease progression, survival, interferon-alpha, prognostic factors
MeSH terms
Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Bone Marrow, Carmustine, Clone Cells, Codon, Combined Modality Therapy, Cyclophosphamide, DNA Mutational Analysis, DNA, Neoplasm, Female, Humans, Immunologic Factors, Male, Melphalan, Middle Aged, Multiple Myeloma, Prednisone, Prognosis, Genes, ras, Polymorphism, Restriction Fragment Length, Vincristine, Life Tables, Survival Analysis, Interferon-alpha, Disease Progression

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