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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The T-cell receptor beta-chain (T beta) gene expression was examined in 16 children with B-lineage acute lymphoblastic leukemia (ALL), including eight patients with rearrangement of the T beta gene as well as immunoglobulin (Ig) heavy chain gene rearrangement. In contrast to the 1.3 kb full-length transcripts of the T beta observed in T-lineage leukemia and lymphoma cells, no transcript of the T beta gene was detected in 10 patients, including four with T beta gene rearrangement. Low levels of T beta transcripts were found in three patients with T beta gene rearrangement and two patients without T beta gene rearrangement, but those transcripts were truncated. In contrast to those findings, a single patient with T beta gene rearrangement showed abundant 1.3 kb T beta transcripts. These data indicate that T beta gene expression is not restricted to T-lineage cells and demonstrate the heterogeneity of B-lineage ALL at the expression level of the T beta gene. Our findings also suggest that T beta gene expression is not always accompanied with T beta gene rearrangement.
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PMID:T-cell receptor beta-chain gene expression in B-lineage acute lymphoblastic leukemia. 313 Dec 84

We have performed gene rearrangement studies on the leukemic blasts of a patient with acute pre-B-cell leukemia. The patient had a 5 year history of follicular lymphoma, which developed into acute pre-B-cell leukemia. The leukemic blasts revealed a karyotype with two translocations, t(8; 14) and t(14; 18), characteristic for Burkitt's lymphoma and follicular lymphoma. The cells are TdT positive, do not possess surface immunoglobulin, and they show immunoglobulin gene rearrangement. The mu heavy chain and kappa light chain constant (C mu and C kappa) loci are deleted, while the gamma and lambda light chain constant (C gamma and C lambda) region genes are rearranged. Both alleles of the heavy chain joining segment (JH) are rearranged on chromosome 14q+, one of them with the bcl-2 oncogene from chromosome 18. The breakpoint of the t(14; 18) translocation occurs in the major breakpoint cluster region in the 3' untranslated region of bcl-2. On chromosome 8 a c-myc rearrangement was mapped immediately 5' to the c-myc first exon in a region involved in sporadic Burkitt lymphoma. The data are consistent with our previous hypothesis on the evolution of B-cell malignancies: a rare pre-B cell develops a t(14; 18) translocation during immunoglobulin VDJ joining that results in an expansion of a follicular lymphoma clone carrying an activated bcl-2 gene. Within the clone of pre-B cells a second translocation, t(8; 14), occurs during heavy chain isotype switching that results in the deregulation of the c-myc involved in the translocation.
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PMID:Pre-B-cell leukemia with a t(8; 14) and a t(14; 18) translocation is preceded by follicular lymphoma. 313 17

A case of plasma cell leukaemia of non-producer type is described. The patient presented with typical clinical features of plasma cell myeloma, including multiple osteolytic lesions, hypercalcaemia, renal failure and reduced polyclonal immunoglobulins, except that M-component was not detected in either the serum or urine. Morphological examinations showed a plasmacytoid appearance of the neoplastic cells, while immunological studies failed to detect cytoplasmic immunoglobulin or secretory capacity. The surface phenotype of CD38+, PCA-1+, DR-, CD20-, CD24-, CD9-, CD10- and surface immunoglobulin- was compatible with mature plasma cells. Chromosomal analysis showed the 14q+ marker due to translocation (6;14) and deletion of the short arm of chromosome 1. Analysis of immunoglobulin genes revealed the presence of heavy chain gene rearrangement, but the light chain genes, both kappa and lambda, remained in germline configuration. Such defective immunoglobulin gene rearrangement may be responsible for the failure of immunoglobulin biosynthesis and secretion by the neoplastic plasma cells. Furthermore, it is suggested that the morphological and phenotypic development of B cells may not necessarily depend on immunoglobulin light chain gene rearrangement, and that the oncogenic event in myeloma may occur at an earlier stage of B cell differentiation.
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PMID:Plasma cell leukaemia of non-producer type with missing light chain gene rearrangement. 313 42

Rearrangement of the beta and gamma chain genes of the TCR gene complex and of the Ig heavy chain genes were examined in three cases of childhood acute mixed lineage leukaemia. Blast cells, classified morphologically as acute lymphoblastic leukaemia (ALL) in one child and acute non-lymphocytic leukaemia (ANLL) in the other two, all co-expressed markers associated with both T (CD7, TdT) and myeloid (CD33) cells. Cytogenetic analysis detected abnormalities associated with myeloid leukaemia. Immunoglobulin heavy chain genes were not rearranged in two patients but a novel rearrangement was seen in the third. No rearrangement of the beta or gamma chains of the T-cell receptor complex were seen. Acute mixed lineage leukaemia may thus arise from a pluripotent precursor cell capable of both lymphoid and myeloid differentiation.
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PMID:Rearrangement of T-cell receptor and immunoglobulin heavy chain genes in childhood acute mixed lineage leukaemia. 314 5

Studies of acute leukemia with the 4;11 translocation have yielded conflicting results regarding the lineage of the cell of origin in this disease. To investigate this issue further, we have examined the state of immunoglobulin genes in tumor cells from two affected patients, immunophenotyped their leukemic cells using a number of monoclonal antibody reagents with specificities for lymphoid or myelomonocytic antigens, and examined the malignant cells by electron microscopy. DNA was extracted from leukemic bone marrow cells and hybridized with radiolabeled DNA fragment probes specific for the constant region of immunoglobulin heavy chain and kappa and lambda light chain genes. Autoradiographs revealed rearrangement of both allelic heavy chain genes, but a germline configuration of light chain genes in both cases. Surface marker analysis showed that blasts from both patients expressed HLA-DR and the myeloid antigens Leu-M1, 1C2, 2D1, and 4B3, but lacked common acute lymphocytic leukemia antigen or T antigens. Furthermore, they did not have sheep erythrocyte receptors nor did they express surface or cytoplasmic immunoglobulin or B cell precursor determinants. Electron microscopy analysis showed that blast cells from patient 1 exhibited numerous monoribosomes, polyribosomes, and isolated strands of rough endoplasmic reticulum in their cytoplasm. These ultrastructural features are characteristic for both common acute lymphocytic leukemia and pre-B-ALL cells, but not for T-ALL or acute myelogenous leukemia cells. Peroxidase was undetectable in cells from both patients. Our study suggests that this disorder represents a unique subtype of leukemia. The cell of origin may be an early B cell progenitor that shares certain surface antigens with myeloid cells or a stem cell with the potential for both lymphoid and myelomonocytic differentiation.
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PMID:Acute leukemias associated with the 4;11 chromosome translocation have rearranged immunoglobulin heavy chain genes. 315 45

We analyzed 50 B cell lymphoma samples by Southern blot analysis, using the bcl-1 and heavy chain immunoglobulin (JH) probes with two or more restriction endonucleases. All samples showed JH rearrangement, and three samples (two diffuse small lymphocytic lymphomas and one diffuse large cell lymphoma probably transformed from a diffuse small lymphocytic lymphoma) demonstrated rearranged bcl-1 sequences. The three samples showed the t(11;14)(q13;q32) chromosome translocation, and all three contained rearranged JH fragments that comigrated with the rearranged bcl-1 fragment. The breakpoint of the translocation occurred within a 1.6-kb region on chromosome 11 in the three cases. Two of the three patients had primary refractory disease. Two of the three patients had gastrointestinal involvement. Bcl-1 rearrangement may identify an unusual subset of patients with primary refractory disease with gastrointestinal involvement. It may also describe a unique subset of large cell lymphoma patients transformed from diffuse small cell histology.
Leukemia 1988 Jun
PMID:Bcl-1 gene rearrangements in B cell lymphoma. 325 59

Plasmacellular hyperplasia in lymphoid tissue was found in 4 out of 9 patients 1-6 months after allogeneic bone marrow transplantation as treatment for leukaemia. In the plasma cell populations, 13-85% expressed a single immunoglobulin light and heavy chain isotype (monotypic Ig expression). DNA analysis, using a DNA probe specific for heavy chain JH gene segments and for light chains, did not reveal the presence of clonally restricted B lymphocytes. The patients' sera lacked homogeneous immunoglobulins. We conclude that plasmacellular hyperplasia found after allogeneic bone marrow transplantation represents a polyclonal B-cell expansion- with a restriction in Ig isotype.
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PMID:Expression of restricted immunoglobulin isotypes in plasmacellular hyperplasia after allogeneic bone marrow transplantation. 331 86

The nature of the cells in 21 cases of acute leukaemia with blasts which were undifferentiated by light microscopy criteria was investigated by immunophenotyping, ultrastructural cytochemistry and DNA analysis. Two groups of cases were recognized. Fourteen cases were negative with B and T lymphoid markers and expressed one or two myeloid antigens detected by the monoclonal antibodies (McAb) MCS2 (CD13) and MY9 (CD33). Peroxidase activity was demonstrated at ultrastructural level by the method of Roels on unfixed cells in eight out of 10 cases; rearrangement of the immunoglobulin (Ig) genes was demonstrated in one of the three cases investigated. These cases are proliferations of early, MO, myeloblasts which can only be recognized by immunological and ultrastructural cytochemical methods. The remaining seven cases revealed a complex phenotype with expression of myeloid and lymphoid antigens. Peroxidase activity was detected in blasts from two cases with rearrangement of the Ig-heavy chain gene; in one of them the T cell receptor beta and gamma chain genes were also found in rearranged configuration. This group comprises cases of biphenotypic and mixed acute leukaemia which probably involve multipotent stem cells. This study demonstrates that the expression of myeloid antigens on blast cells parallels closely the presence of peroxidase activity and that lymphoid markers correlate with gene rearrangements at DNA level. Our findings are reassuring with respect to the specificity of the antimyeloid McAb for the diagnosis of cases which are unclassifiable by conventional methods.
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PMID:The role of ultrastructural cytochemistry and monoclonal antibodies in clarifying the nature of undifferentiated cells in acute leukaemia. 339 Mar 93

Progression of more differentiated to less differentiated malignant phenotypes has been described infrequently during the natural evolution or at relapse of treated hematopoietic malignancies. This report describes an unusual instance of immunophenotypic transformation from an immunologically undifferentiated acute leukemia to a leukemia that at relapse possessed morphologic and immunologic markers characteristic of a Burkitt's-like acute lymphoblastic leukemia. A 26-year-old man initially presented with pancytopenia and a bone marrow diffusely replaced with blast cells morphologically most consistent with a French-American-British L2 subclassification. The surface immunophenotype of the blasts at diagnosis showed HLA-DR surface antigen but no myeloid, lymphoid, or immunoglobulin determinants. Despite successful induction and ongoing consolidation chemotherapy, the patient had a relapse five months after diagnosis; blast cells at relapse demonstrated marked cytoplasmic vacuolation consistent with a Burkitt's-like L3 acute lymphoblastic transformation. Immunophenotypic analysis revealed the presence of restricted immunoglobulin determinants (mu heavy chain and kappa light chain), as well as two separate B lineage surface determinants (BA-1 and B-1). Immunophenotypic transformations may reflect the presence of either a multiclonal or multipotent leukemic population; documentation of the frequency of such transformations and genomic analysis of the transformed subpopulations may be helpful in furthering the understanding of molecular mechanisms involved in leukemogenesis.
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PMID:Immunophenotypic transformation from acute undifferentiated leukemia to Burkitt's-like acute lymphoblastic leukemia. 346 12

The use of probes to genes (IG and TCRB) encoding immunoglobulins (IG) and the beta chain of the T-cell antigen receptor (TCRB), respectively, have become a sensitive means to assess clonality and lineage in lymphoid malignancies. It has become apparent that some individual cases show rearrangements of both IG and TCRB genes. In an attempt to more accurately define cell lineage we have analyzed cells from patients with B- or T-cell leukemia (n = 26) at various stages of maturation with probes to two additional TCR genes, TCRG and TCRA (encoding the TCR gamma and alpha chains, respectively), as well as the IG heavy chain joining region (IGHJ) and TCRB genes. On Southern blot analysis, the mature T-cell leukemia cells studied had rearranged TCRG and TCRB while IGHJ remained as in the germ line. The mature B-cell leukemia cells studied had rearranged IGHJ with germ-line TCRG and TCRB. These data suggest that, in the majority of more mature leukemias, cells have rearranged IG or TCR genes but not both. In contrast, cells from five of nine precursor B-cell leukemia patients and cell lines from one of four precursor T-cell leukemia patients had rearranged both IGHJ and TCR genes. TCRG and TCRB mRNAs were expressed in the cells of precursor T- but not B-cell leukemia patients studied. The spectrum of leukemia cells studied within the T-cell series permitted an assessment of the order of TCR gene rearrangements. Two of 13 patients had cells with germ-line TCRG and TCRB, 2 patients had cells with rearranged TCRG alone, and the remainder had cells with rearranged TCRG and TCRB. TCRG and TCRB mRNAs were expressed in precursor T-cell leukemia cells, whereas TCRB and TCRA were expressed in mature T-cell leukemia cells. These results parallel observations from mouse studies on gene expression and support the view of a hierarchy of TCR gene rearrangements in T-lymphocyte ontogeny. TCRG genes are rearranged first, subsequently TCRB genes are rearranged, followed by TCRA gene activation.
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PMID:Immunoglobulin and T-cell receptor gene rearrangement and expression in human lymphoid leukemia cells at different stages of maturation. 346 80


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