scholarly journals Detection of two distinct malignant B cell clones in a single patient using anti-idiotype monoclonal antibodies and immunoglobulin gene rearrangement

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1017-1021
Author(s):  
SL Giardina ◽  
RW Schroff ◽  
CS Woodhouse ◽  
DW Golde ◽  
RK Oldham ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Lymph Node ◽  
B Cell ◽  
Gene Rearrangement ◽  
Leukemic Cells ◽  
Cell Populations ◽  
Immunoglobulin Gene ◽  
Immunoglobulin Gene Rearrangement ◽  
Lymph Node Cells

Immunoglobulin gene rearrangement analysis and somatic cell hybridization techniques were used to examine the malignant cell population in an unusual patient with hairy cell leukemia and macroglobulinemia (N Engl J Med 296:92, 1977). Although previous investigations suggested that the IgM macroglobulin was secreted by the circulating leukemia cells, anti-idiotype monoclonal antibodies raised to the IgM macroglobulin failed to react with the malignant cells in the circulation and bone marrow. In contrast, approximately 50% of the mononuclear cells from an enlarged inguinal lymph node reacted strongly with the anti-idiotype antibodies. Subsequent reanalysis of all cell populations demonstrated that whereas the circulating and bone marrow cells were IgM kappa-bearing, the macroglobulin was IgM gamma-bearing and the lymph node cells were evenly divided among IgM kappa-bearing and IgM gamma-bearing. Immunofluorescence flow cytometry indicated that those lymph node cells that reacted strictly with the anti-idiotype antibody were IgM gamma-bearing, demonstrating that they were the source of macroglobulin. An analysis of immunoglobulin gene DNA confirmed the coexistence of two distinct malignant B cell populations in the lymph node and indicated that the IgM kappa-bearing lymph node cells were identical to the circulating and bone marrow leukemic cells.

scholarly journals Detection of two distinct malignant B cell clones in a single patient using anti-idiotype monoclonal antibodies and immunoglobulin gene rearrangement

Blood ◽  
1985 ◽  
Vol 66 (5) ◽  
pp. 1017-1021 ◽  
Author(s):  
SL Giardina ◽  
RW Schroff ◽  
CS Woodhouse ◽  
DW Golde ◽  
RK Oldham ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Monoclonal Antibodies ◽  
Lymph Node ◽  
B Cell ◽  
Gene Rearrangement ◽  
Leukemic Cells ◽  
Cell Populations ◽  
Immunoglobulin Gene ◽  
Immunoglobulin Gene Rearrangement ◽  
Lymph Node Cells

Abstract Immunoglobulin gene rearrangement analysis and somatic cell hybridization techniques were used to examine the malignant cell population in an unusual patient with hairy cell leukemia and macroglobulinemia (N Engl J Med 296:92, 1977). Although previous investigations suggested that the IgM macroglobulin was secreted by the circulating leukemia cells, anti-idiotype monoclonal antibodies raised to the IgM macroglobulin failed to react with the malignant cells in the circulation and bone marrow. In contrast, approximately 50% of the mononuclear cells from an enlarged inguinal lymph node reacted strongly with the anti-idiotype antibodies. Subsequent reanalysis of all cell populations demonstrated that whereas the circulating and bone marrow cells were IgM kappa-bearing, the macroglobulin was IgM gamma-bearing and the lymph node cells were evenly divided among IgM kappa-bearing and IgM gamma-bearing. Immunofluorescence flow cytometry indicated that those lymph node cells that reacted strictly with the anti-idiotype antibody were IgM gamma-bearing, demonstrating that they were the source of macroglobulin. An analysis of immunoglobulin gene DNA confirmed the coexistence of two distinct malignant B cell populations in the lymph node and indicated that the IgM kappa-bearing lymph node cells were identical to the circulating and bone marrow leukemic cells.

Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus

1993 ◽  
Vol 5 (6) ◽  
pp. 647-656 ◽  
Author(s):  
Jianzhu Chen ◽  
Mary Trounstine ◽  
Frederick W. Alt ◽  
Faith Young ◽  
Carole Kurahara ◽  
...  
Keyword(s):  
B Cell ◽  
Gene Rearrangement ◽  
Immunoglobulin Gene ◽  
Targeted Deletion ◽  
Immunoglobulin Gene Rearrangement ◽  
Deficient Mice

Clonality of Cutaneous B-Cell Infiltrates Determined by Microdissection and Immunoglobulin Gene Rearrangement

1999 ◽  
Vol 8 (4) ◽  
pp. 176-182 ◽  
Author(s):  
Sabina Signoretti ◽  
Michael Murphy ◽  
Pietro Puddu ◽  
John F. DeCoteau ◽  
Tullio Faraggiana ◽  
...  
Keyword(s):  
B Cell ◽  
Gene Rearrangement ◽  
Immunoglobulin Gene ◽  
Immunoglobulin Gene Rearrangement

scholarly journals Clinical and laboratory characteristics of acute leukemia with the 4;11 translocation

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 689-697 ◽  
Author(s):  
J Mirro ◽  
G Kitchingman ◽  
D Williams ◽  
GJ Lauzon ◽  
CC Lin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Acute Leukemia ◽  
B Cell ◽  
Heavy Chain ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Immunoglobulin Gene ◽  
Immunoglobulin Gene Rearrangement

Abstract This report describes the clinical and laboratory features of seven cases of acute leukemia associated with the 4;11 chromosomal translocation. All seven children had acute lymphoblastic leukemia by standard morphologic and cytochemical criteria. Leukemic blasts from six of seven patients were terminal deoxynucleotidyl transferase- positive. Immunologic phenotyping suggested the leukemias were of B cell origin; blasts from five patients expressed HLA-DR and p24 (CD-9 antibody), blasts from three patients expressed B4 (CD-19), and blasts from two patients expressed the common acute lymphoblastic leukemia antigen (CD-10). One patient's leukemic blasts contained cytoplasmic immunoglobulin. Analysis of DNA from four of five patients demonstrated additional evidence of B cell differentiation with heavy-chain immunoglobulin gene rearrangement. When DNA from the four patients with heavy-chain immunoglobulin gene rearrangement was analyzed, one patient's DNA demonstrated light-chain immunoglobulin gene rearrangement. However, flow cytometric analysis of blasts from three patients showed the simultaneous expression of the lymphoid-associated antigen B4 (CD-19) and the myeloid-associated antigen My-1 (X-Hapten). Electron microscopic examination of blasts from one patient that expressed both lymphoid- and myeloid-associated antigens demonstrated ultrastructural characteristics of both lineages. These findings suggest that acute leukemia with the t(4;11) abnormality has mixed lineage characteristics as a result of leukemogenesis in a multipotential progenitor cell or aberrant gene expression later in differentiation. Furthermore, serial analysis of karyotype, immunophenotype, and heavy-chain immunoglobulin genes revealed changes in these biologic markers over time, suggesting continued chromosome rearrangement and gene modulation after the leukemogenic event in cells with the t(4;11).

Heavy chain immunoglobulin gene rearrangement in acute nonlymphocytic leukemia

Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 1023-1027
Author(s):  
U Rovigatti ◽  
J Mirro ◽  
G Kitchingman ◽  
G Dahl ◽  
J Ochs ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Heavy Chain ◽  
Gene Rearrangement ◽  
Leukemia Cell ◽  
Leukemic Cell ◽  
Immunoglobulin Gene ◽  
Acute Nonlymphocytic Leukemia ◽  
Lymphoid Leukemia ◽  
Immunoglobulin Gene Rearrangement

Samples of leukemic cell DNA from 14 children with acute nonlymphocytic leukemia (ANLL) and 4 human myeloid leukemia cell lines were analyzed for rearrangement in the heavy chain region of the immunoglobulin gene. The diagnosis of ANLL was confirmed in all patients by morphological, cytochemical, and immunologic studies. By restriction endonuclease digestion and hybridization with cloned heavy chain immunoglobulin gene probes for the constant (Cmu) and joining (JH) regions, the DNA of 2 patients and 1 cell line (ML-1) was found to contain rearrangements. The DNA from the remaining 12 patients and 3 cell lines was not rearranged (germline configuration). Both patients with apparent immunoglobulin gene rearrangement achieved complete remission on therapy for ANLL. Immunoglobulin gene rearrangement in phenotypically defined ANLL suggests (1) that such changes may not be limited to lymphoid leukemia of B cell lineage, or (2) that, in some patients, the leukemic transforming event may involve stem cells capable of both B cell and myeloid differentiation.

scholarly journals Unusual patterns of immunoglobulin gene rearrangement and expression during human B cell ontogeny: human B cells can simultaneously express cell surface kappa and lambda light chains.

1993 ◽  
Vol 178 (1) ◽  
pp. 139-149 ◽  
Author(s):  
M E Pauza ◽  
J A Rehmann ◽  
T W LeBien
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Cell Surface ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Gene Rearrangement ◽  
Immunoglobulin Gene ◽  
Human B Cells ◽  
Sds Page

Immunoglobulin gene rearrangement during mammalian B cell development generally follows an ordered progression, beginning with heavy (H) chain genes and proceeding through kappa and lambda light (L) chain genes. To determine whether the predicted kappa-->lambda hierarchy was occurring in vitro, we generated Epstein-Barr virus-transformed cell lines from cultures undergoing human pre-B cell differentiation. A total of 143 cell lines were established. 24 expressed cell surface mu/lambda by flow cytometry and were clonal by Southern blotting. Surprisingly, two of the mu/lambda-expressing cell lines contained both kappa alleles in germline configuration, and synthesis/expression of conventional lambda L chains was directly proven by immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in one of them. Thus, human fetal bone marrow B lineage cells harbor the capacity to make functional lambda L chain gene rearrangements without rearranging or deleting either kappa allele. A third unusual cell line, designated 30.30, was observed to coexpress cell surface kappa and lambda L chains associated with mu H chains. The 30.30 cell line had a diploid karyotype, a single H chain rearrangement, both kappa alleles rearranged, and a single lambda rearrangement. Immunoprecipitation/SDS-PAGE confirmed that 30.30 cells synthesized and expressed kappa and lambda L chains. Multiparameter flow cytometry was used to demonstrate the existence of kappa+/lambda+ cells in fetal bone marrow and fetal spleen at frequencies of 2-3% of the total surface Ig+ B cell population. The flow cytometry data was confirmed by two-color immunofluorescence microscopy. The existence of normal human B cells expressing cell surface kappa and lambda refutes the widely accepted concept that expression of a single L chain isotype is immutable. The kappa+/lambda+ cells may represent transients undergoing L chain isotype switching.

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