Original Articles
Cytogenetics in Multiple Myeloma: A Multicenter Study of 24 Patients with t(11;14)(q13;q32) or Its Variant

https://doi.org/10.1016/S0165-4608(97)00469-XGet rights and content

Abstract

Twenty-two patients with multiple myeloma (MM) with a classical t(11;14)(q13;q32) and two complex variants also involving 11q13 and 14q32 regions are reported. We show that t(11;14) (q13;q32) is predominantly noticed in stages II and III and never in stage I patients. Translocation (11;14)(q13;q32) is predominantly observed in hypodiploid or pseudodiploid clones associated with total or partial monosomy of chromosome 13 and additional structural changes in chromosome 1. These translocations may be discovered not only in standard cultures (24–48 hours) without stimulation, but also in cytokine-stimulated cultures (granulocyte macrophage colony-stimulating factor and interleukin 6). The t(11;14)(q13;q32) as a primary or secondary event in MM is discussed, because, in one patient, it was only discovered at relapse.

Introduction

Cytogenetic studies performed in multiple myeloma (MM) are relatively rare and difficult because of the low proliferation rate of plasma cells. The incidence of karyotypically abnormal patients is approximately 40% in most of large series reported 1, 2, 3, 4, 5, 6, 7, ranging from 20% to 60%. More recently, cytogenetic studies have been performed on bone marrow cells after long-term cultures (6–7 days) with granulocyte macrophage colony-stimulating factor (GM-CSF) plus interleukin 6 (IL6) 8, 9 to improve myeloma cell growth. Thus, the percentage of abnormal clones reached 50% in patients studied at diagnosis when high concentrations of both aforementioned cytokines were used [8], enhancing the discovery of abnormal cells at diagnosis.

Previous cytogenetic studies revealed that translocations involving band 14q32 were a nonrandom structural abnormality in MM and plasma cell leukemia (PCL), occurring at a frequency of 30–50% of abnormal karyotypes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13; t(11;14)(q13;q32) was reported to be the most frequent 14q32 translocation (10–15% of abnormal karyotypes). However, most published results were based on isolated cases or observed in a few patients in large series. In the present multicentric study, we reviewed cytogenetic characteristics of 24 patients with MM or PCL: all patients showed a t(11;14)(q13;q32) or a variant of this translocation.

Section snippets

Materials and methods

Cytogenetic data are presented for 28 bone marrow (BM) samples from 24 MM patients karyotyped in the past 6 years. Diagnoses were performed according to Durie [14]. Cultivation conditions of BM cells varied according to the length of time of cultivation: a 24–48 hour culture without stimulation (13 patients) or 6–7 days with stimulation by 30 ng/mL GM-CSF plus 2000 IU/ml IL6 as previously described 8, 15 (11 patients). Four patients were karyotyped twice. Chromosomes were identified by RHG or

Patients

Patients were recruited from four centers in France and Belgium. Among the 24 patients, 13 were male and 11 were female; 17 were newly diagnosed MM and 7 were in relapse.

The majority of patients (pts) were at stage II (2 pts) or stage III (21 pts). Only one patient had PCL. M component isotype was as follows: IgG, 8 pts; IgA, 6 pts; IgD, 2 pts; Bence Jones, 7 pts, nonexcreting, 1 pt. Light chain was kappa in 9 pts and lambda in 14 pts.

Results

Major clinical, cytological and cytogenetic data of the 24 MM cases with a t(11;14)(q13;q32) anomaly are summarized in Table 1. Twenty-two patients showed the classical t(11;14)(q13;q32), whereas two patients had variants of t(11;14): a three-way translocation (11;17;14)(q13;p11;q32) (case 10) and a four-way translocation (11;9;12;14)(q13; p21;q24;q32) (case 22) (Fig. 1), associated with numerical and structural changes including a der(1;16)(p10;q10). The association of t(11;14) with other

Discussion

The most important structural change in MM and PCL is a 14q+ chromosome change found in about 20–30% of all patients [17]. The counterpart chromosome involved in the translocation with chromosome 14 is not always clearly identified, but t(11;14)(q13;q32) is the most frequent 14q32 translocation, occurring in about 10–25% of cases with an abnormal clone 1, 2, 5, 7, 8.

Even though in the majority of cases t(11;14) is balanced, in some cases 14q+ markers with extra material from the long arm of

Acknowledgements

The authors gratefully acknowledge the excellent technical assistance of A. Delcroix, M.F. Decoene, and I. Morel, and A. Vanderhaegen for preparing figures. This work was supported by grants from the Comité du Nord de la Ligue Nationale Contre le Cancer, the INSERM, and the Fondation Contre les Leucémies.

References (34)

  • W. Liang et al.

    Karyotypic abnormalities and clinical aspects of patients with multiple myeloma and related paraproteinemic disorders

    Cancer

    (1979)
  • A. Ferti et al.

    Cytogenetic study in multiple myeloma

    Cancer Genet Cytogenet

    (1983)
  • J.P. Lewis et al.

    Nonrandom chromosomal aberrations associated with multiple myeloma

    Hematol Oncol

    (1984)
  • K.C. Chen et al.

    Analysis of G banded karyotypes in myeloma cells

    J Clin Pathol

    (1986)
  • Y. Ueshima et al.

    Cytogenetic studies and clinical aspects of patients with plasma cell leukemia and leukemic macroglobulinemia

    Cancer Res

    (1983)
  • M. Taniwaki et al.

    Non-random chromosomal rearrangements and their implications in clinical features and outcome of multiple myeloma and plasma cell leukemia

    Leuk Lymphoma

    (1996)
  • I.M. Liss et al.

    Occurrence and type of chromosomal abnormalities in consecutive malignant monoclonal abnormalitiescorrelation with survival

    Cancer Genet Cytogenet

    (1988)

    • Cited by (0)

    View full text
    Copyright © 1998 Elsevier Science Inc. All rights reserved.