Characterization of a novel malignant B cell line with t(14;18) and t(4;11) established from a patient with acute monoblastic leukemia.
The severe combined immunodeficient (SCID) mouse model is an important tool with which to study new strategies for treating hematologic neoplasia. For these experiments, a large number of human cell lines growing in SCID mice are a prerequisite. We describe a new Epstein-Barr virus (EBV)-positive B cell line, designated BEVA, with a complex karyotype including translocations t(14:18)(q32;q21) and t(4;11) (q21;q23) that meets this need. As demonstrated by Southern blot analysis, BCL2 at 18q21, but not MLL/ALL1 at 11q23, was involved in these translocations. BEVA cells coexpressed lymphoid (IgG-kappa, CD19, CD20, CD21, and CD24) and myeloid (CD11b, CD15, and CDw65) markers. Interestingly, the cell line was established from the bone marrow culture of a patient with acute myeloid leukemia (AML). Examination of bone marrow biopsy specimens suggested the presence of non-Hodgkin's lymphoma (NHL) in this patient in addition to AML. In vitro and in vivo growth characteristics of the BEVA cell line were compared with the previously described EBV-positive B cell line DoHH2, also carrying a translocation t(14;18)(q32;q21). These DoHH2 cells additionally expressed CD10, whereas, in contrast to BEVA cells, only a small population of DoHH2 cells showed expression of CD44. Both cell lines showed similar growth characteristics in vitro, but reacted differently to cytokines, including interleukin (IL)-4, IL-6, IL-7, and alpha-interferon (IFN). Upon inoculation in SCID mice, marked differences were observed in the dissemination patterns of the BEVA or DoHH2 cells. Although both cell lines circulated in the blood and were predominantly found in murine bone marrow and lymphoid tissues, DoHH2 cells infiltrated the murine spleens, whereas BEVA cells could only rarely be detected in these tissues. In contrast to DoHH2 cells, BEVA cells gave rise to tumor masses in liver, kidney, and para-aortal or mesenteric lymph nodes. The relationship between these in vitro differences and the observed differences in dissemination of both cell lines is discussed.
de Kroon
J F
JF
Department of Hematology, University Medical Center, Leiden, The Netherlands.
Kluin-Nelemans
H C
HC
Kluin
P M
PM
Schuuring
E
E
van Bergen
C A
CA
Oving
I
I
Wessels
H
H
Willemze
R
R
Falkenburg
J H
JH
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations / Q000235:genetics* / Q000473:pathology; D025063:Chromosome Disorders; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D002894:Chromosomes, Human, Pair 4; D006410:Hematopoiesis; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D007948:Leukemia, Monocytic, Acute / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D014178:Translocation, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured