Clinical and biologic implications of recurrent genomic aberrations in myeloma

Rafael Fonseca, Emily Blood, Montserrat Rue, David Harrington, Martin M. Oken, Robert A. Kyle, Gordon W. Dewald, Brian Van Ness, Scott A. Van Wier, Kimberly J. Henderson, Richard J. Bailey, Philip R. Greipp

Research output: Contribution to journalArticle

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Abstract

Nonrandom recurrent chromosomal abnormalities are ubiquitous in multiple myeloma (MM) and include, among others, translocations of the immunoglobulin heavy chain locus (IgH). IgH translocations in MM result in the up-regulation of oncogenes, and include more commonly t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23). Based on the recurrent nature of these translocations and their finding since the early stages of the plasma cell (PC) disorders, we hypothesized that they would confer biologic and clinical variability. In addition, deletions of 13q14 and 17p13 have also been associated with a shortened survival. We used cytoplasmic Ig-enhanced interphase fluorescent in situ hybridization to detect deletions (13q14 and 17p13.1), and translocations involving IgH in 351 patients treated with conventional chemotherapy entered into the Eastern Cooperative Oncology Group clinical trial E9486/9487. Translocations were frequently unbalanced with loss of one of the derivative chromosomes. The presence of t(4; 14)(p16;q32) (n = 42; 26 vs 45 months, P < .001), t(14;16)(q32;q23) (n = 15; 16 vs 41 months, P = .003), - 17p13 (n = 37; 23 vs 44 months, P = .005), and - 13q14 (n = 176; 35 vs 51 months, P = .028) were associated with shorter survival. A stratification of patients into 3 distinct categories allowed for prognostication: poor prognosis group (t(4;14)(p16;q32), t(14; 16)(q32;q23), and - 17p13), intermediate prognosis (- 13q14), and good prognosis group (all others), with median survivals of 24.7, 42.3, and 50.5 months, respectively (P < .001). This molecular cytogenetic classification identifies patients into poor, intermediate, and good risk categories. More importantly it provides further compelling evidence that MM is composed of subgroups of patients categorized according to their underlying genomic aberrations.

Original languageEnglish (US)
Pages (from-to)4569-4575
Number of pages7
JournalBlood
Volume101
Issue number11
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

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Immunoglobulin Heavy Chains
Oncology
Chemotherapy
Chromosomes
Aberrations
Multiple Myeloma
Derivatives
Plasmas
Survival
Interphase
Plasma Cells
Fluorescence In Situ Hybridization
Oncogenes
Cytogenetics
Chromosome Aberrations
Up-Regulation
Clinical Trials
Drug Therapy

ASJC Scopus subject areas

  • Hematology

Cite this

Fonseca, R., Blood, E., Rue, M., Harrington, D., Oken, M. M., Kyle, R. A., ... Greipp, P. R. (2003). Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood, 101(11), 4569-4575. https://doi.org/10.1182/blood-2002-10-3017

Clinical and biologic implications of recurrent genomic aberrations in myeloma. / Fonseca, Rafael; Blood, Emily; Rue, Montserrat; Harrington, David; Oken, Martin M.; Kyle, Robert A.; Dewald, Gordon W.; Van Ness, Brian; Van Wier, Scott A.; Henderson, Kimberly J.; Bailey, Richard J.; Greipp, Philip R.

In: Blood, Vol. 101, No. 11, 01.06.2003, p. 4569-4575.

Research output: Contribution to journalArticle

Fonseca, R, Blood, E, Rue, M, Harrington, D, Oken, MM, Kyle, RA, Dewald, GW, Van Ness, B, Van Wier, SA, Henderson, KJ, Bailey, RJ & Greipp, PR 2003, 'Clinical and biologic implications of recurrent genomic aberrations in myeloma', Blood, vol. 101, no. 11, pp. 4569-4575. https://doi.org/10.1182/blood-2002-10-3017
Fonseca R, Blood E, Rue M, Harrington D, Oken MM, Kyle RA et al. Clinical and biologic implications of recurrent genomic aberrations in myeloma. Blood. 2003 Jun 1;101(11):4569-4575. https://doi.org/10.1182/blood-2002-10-3017
Fonseca, Rafael ; Blood, Emily ; Rue, Montserrat ; Harrington, David ; Oken, Martin M. ; Kyle, Robert A. ; Dewald, Gordon W. ; Van Ness, Brian ; Van Wier, Scott A. ; Henderson, Kimberly J. ; Bailey, Richard J. ; Greipp, Philip R. / Clinical and biologic implications of recurrent genomic aberrations in myeloma. In: Blood. 2003 ; Vol. 101, No. 11. pp. 4569-4575.
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AU - Kyle, Robert A.

AU - Dewald, Gordon W.

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N2 - Nonrandom recurrent chromosomal abnormalities are ubiquitous in multiple myeloma (MM) and include, among others, translocations of the immunoglobulin heavy chain locus (IgH). IgH translocations in MM result in the up-regulation of oncogenes, and include more commonly t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23). Based on the recurrent nature of these translocations and their finding since the early stages of the plasma cell (PC) disorders, we hypothesized that they would confer biologic and clinical variability. In addition, deletions of 13q14 and 17p13 have also been associated with a shortened survival. We used cytoplasmic Ig-enhanced interphase fluorescent in situ hybridization to detect deletions (13q14 and 17p13.1), and translocations involving IgH in 351 patients treated with conventional chemotherapy entered into the Eastern Cooperative Oncology Group clinical trial E9486/9487. Translocations were frequently unbalanced with loss of one of the derivative chromosomes. The presence of t(4; 14)(p16;q32) (n = 42; 26 vs 45 months, P < .001), t(14;16)(q32;q23) (n = 15; 16 vs 41 months, P = .003), - 17p13 (n = 37; 23 vs 44 months, P = .005), and - 13q14 (n = 176; 35 vs 51 months, P = .028) were associated with shorter survival. A stratification of patients into 3 distinct categories allowed for prognostication: poor prognosis group (t(4;14)(p16;q32), t(14; 16)(q32;q23), and - 17p13), intermediate prognosis (- 13q14), and good prognosis group (all others), with median survivals of 24.7, 42.3, and 50.5 months, respectively (P < .001). This molecular cytogenetic classification identifies patients into poor, intermediate, and good risk categories. More importantly it provides further compelling evidence that MM is composed of subgroups of patients categorized according to their underlying genomic aberrations.

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