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

Mice transgenic for gamma 2b Ig heavy chain were examined for alterations in B-cell differentiation and endogenous Ig gene rearrangement and expression. Fresh bone marrow from these mice was markedly reduced in BP-1+ cells and there were small reductions in B220+ and sIg+ cells. A-MuLV (Abelson murine leukemia virus) transformants from these bone marrow cells showed little alteration in Ig gene rearrangement and expression when compared to controls, however. Isolation of the B-lymphoid compartment from these mice in vitro using LBMC (lymphoid bone marrow cultures) enabled more detailed characterization of the effects of the transgene. LBMC derived from gamma 2b transgenic mice had similar growth kinetics, but a 4-5-week delay in the expression of endogenous mu Ig in comparison to control cultures. Nucleic acids derived from these early cultures prior to endogenous mu Ig expression showed reduced Ig JH rearrangements, some sterile mu transcription, low levels of BP-1 expression, and virtually undetectable TdT (terminal deoxynucleotidyl transferase) expression. Thus, this gamma 2b transgene appears able to affect early B-lymphocyte development.
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PMID:Delay of early B-lymphocyte development by gamma 2b immunoglobulin transgene: effect on differentiation-specific molecules. 196 16

Ig heavy chain (IgH) J (JH) region organization in 83 human acute leukemias was studied. In 31 of the 35 precursor B acute lymphocytic leukemia (ALL) the rearrangements of the IgH gene involved sites between D regions 5' to DQ52 and JH. The study of the IgH gene organization in 43 T lineage ALL showed nine cases with the rearrangement at the IgJH region, one of which involved the D region 5' to DQ52. When analyzed with another restriction enzyme (BglII), three of the remaining eight showed rearrangement between DQ52 and JH. In the remaining five samples rearrangement of the IgJH region was not shown, but the restriction fragment length polymorphism (RFLP) between MspI sites in 5'DQ52 loci was observed. Thus the RFLP in 5'DQ52 locus was identified and was distinguished from the recombination between DQ52 and JH in non-B lineage leukemias.
Leukemia 1990 Jun
PMID:Molecular analysis of 5' J region of immunoglobulin heavy chain gene in human acute leukemias. 197 69

Morphological, immunological, cytogenetic, and molecular features of 28 cases of acute mixed lineage leukemia (AMLL), defined by the co-expression of lymphoid and myeloid cell surface antigens, were correlated in a multiparameter study. These 28 cases were identified in a series of 260 consecutive acute leukemia cases occurring predominantly in adults and were subdivided into 18 cases of AMLL with myeloid morphology and cytochemistry (AMLL-AML) and 10 cases of AMLL with lymphoid morphology and cytochemistry (AMLL-ALL). A lack of correlation was observed between the expression of B- or T-cell associated antigens with the presence of the expected immunoglobulin (Ig) or T-cell receptor (TCR) gene rearrangements in the AMLL cases with myeloid morphology. Only three of the 18 total AMLL-AML cases, each co-expressing B- and myeloid-associated cell surface antigens (B/My), had Ig heavy chain gene rearrangements with or without rearrangements of TCR genes. Ig light chain genes remained in the germline configuration. Strikingly, these three cases were the only AMLL-AML cases in our series to have the Philadelphia (Ph) chromosome translocation t(9;22)(q34;q11), suggesting that a significant percentage of acute leukemias with myeloid morphology and gene rearrangements may be Ph+ AMLL. The fact that three of the 10 B/My AMLL-AML cases in our series were Ph+ suggests that there may be an increased frequency of Ph chromosome, a translocation associated with a poor prognostic outcome, in B/My AMLL-AML occurring in the adult population. Although most AMLL cases with lymphoid morphology had Ig and TCR gene rearrangements associated with a variety of immunophenotypes and karyotypes, two Ph+ AMLL-ALL cases had many similar features (B/My immunophenotype; IgH with or without TCR rearrangements; Ig light chain genes germline) to their Ph+ AMLL-AML counterparts. However, the Ph+ AMLL-ALL cases differed from the Ph+ AMLL-AML cases by the expression of a more mature B-cell lineage immunophenotype and by their additional cytogenetic changes.
Leukemia 1991 May
PMID:Multiparameter analysis of acute mixed lineage leukemia: correlation of a B/myeloid immunophenotype and immunoglobulin and T-cell receptor gene rearrangements with the presence of the Philadelphia chromosome translocation in acute leukemias with myeloid morphology. 203 59

The ability of recombinant interleukin 2 (rIL2) activated lymphocytes (LAK) to purge BM samples contaminated by tumour cells was evaluated. Human BM mononuclear cells were contaminated with 10% of the lymphoma line CA46 and then cultured in liquid medium containing 1000 U/ml of rIL2 and/or LAK autologous to the used BM. At the end of coculture the growth of residual tumour cells and of CFU-GM were evaluated by clonogenic assay. No tumour cell growth was observed in 5/5 independent experiments after 18 h of coculture with LAK. No significant inhibition of CFU-GM growth was also noted. Subsequently, the effect of LAK on BM obtained from four leukaemic patients and contaminated with 20-50% of their own AML and ALL cells was studied using MAb as a tool for identifying leukaemic cells. LAK eliminated 24-78% of contaminating cryopreserved uncultured autologous leukaemic cells. In five cases the BM was contaminated by a low (2%) amount of ALL cells. In these patients the monoclonal heavy chain rearrangement typical of ALL was no longer visible after coculture with LAK. Evidence for selective tumour cytotoxicity by LAK was confirmed by using autologous BM cells as hot and cold targets in a 51Cr release assay. Finally, successful haematologic reconstitution of lethally irradiated BALB/c mice was obtained using syngeneic BM cocultured with LAK. These results support the investigational use of rIL2 and LAK in the treatment of human leukaemia.
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PMID:Selective purging by human interleukin-2 activated lymphocytes of bone marrows contaminated with a lymphoma line or autologous leukaemic cells. 206 57

To clarify how the v-abl oncogene of Abelson murine leukemia virus contributes to lymphoid tumorigenesis, we introduced the gene linked to an immunoglobulin heavy chain enhancer (E mu) into the mouse germline. Although lymphoid development was not detectably affected in young E mu-v-abl mice, three transgenic lines shared a high predisposition to develop clonal plasmacytomas that secreted IgA or IgG. The unexpected absence of pre-B lymphomas suggests that Abelson virus generates such tumors by infecting an early lymphoid progenitor cell that has not yet activated the heavy chain enhancer. Most plasmacytomas bore a rearranged c-myc gene, apparently as a result of spontaneous translocation to the Igh locus. Moreover, progeny of a cross with analogous E mu-myc mice rapidly developed oligoclonal plasmacytomas. Thus, the collusion of v-abl with c-myc is stage specific, efficiently transforming plasma cells but not pre-B cells or B cells.
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PMID:An E mu-v-abl transgene elicits plasmacytomas in concert with an activated myc gene. 215 83

A 17-year-old male with bilineal hybrid acute leukemia is described. Two-color flow cytometric analysis of blast surface phenotype revealed that there were two groups of blasts which showed either CD 10+ CD 19+ CD 13- CD 33- or CD 10- CD 19- CD 13+ CD 33+, but not both. He developed a complete remission by treatment with vincristine, prednisolone, adriamycin, and L-asparaginase. After 8 months, however, leukemia relapsed and lymphoid blasts were dominant. Cytogenetic analysis at presentation showed 46,XY,t(3;9)(p21;p22), and at relapse it showed 46,XY,t(1;3;9)(1pter----1q32::3p25----3pter;3 qter----3p21::9p22----9pter; 9qter----9p22::3p21----3p25::1q32----1q ter),t(2;19)(p21;q13). Analysis of the heavy chain joining region at diagnosis showed three hybridizing bands, all rearranged, but at relapse only one rearranged band. Analysis of the constant region for the beta T-cell receptor gene (TCR beta) both at diagnosis and at relapse showed one rearranged and one germline band, suggesting that rearrangement of one allele of TCR beta of not only lymphoid but also myeloid blasts occurred. It is considered that the target cell of lymphoid leukemia cells and that of myeloid leukemia cells at diagnosis were the same, which differentiated to two lineages, and the clone which evolved from lymphoid lineage proliferated at relapse.
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PMID:Transformation of bilineal hybrid acute leukemia to acute lymphoid leukemia: a case report with serial analyses of cytogenetics and gene rearrangement. 216 90

We studied the organization of immunoglobulin (Ig) genes and the beta-chain gene of the T cell receptor (TCR) along with the clinical features, immunophenotypes, and karyotypes of 14 children with acute leukemia at diagnosis and relapse. The median time to relapse was 23 months. Eleven children had identical gene rearrangement patterns at diagnosis and relapse. All three patients whose blast cells showed variations in gene rearrangement patterns between diagnosis and relapase also demonstrated a change in the immunophenotype: one from cALLA+ to cALLA- B precursor cell ALL; one from T-ALL to AML; and one showed a marked increase in myeloid characteristics at relapse. Blast cells from these three patients at relapse showed the presence of chromosomal translocations involving 11q23; for two patients, this involved replacement of the original karyotype. We conclude that while most relapses are the result of reemergence of the original clone, new clones that differ in immunophenotype, karyotype, and gene rearrangement are occasionally present at relapse. Relapses may also occur in which the original clone has undergone major changes in gene expression and arrangement of the Ig heavy chain genes in the absence of karyotypic replacement.
Leukemia 1990 Nov
PMID:Alterations in immunoglobulin or T cell receptor gene rearrangement at relapse: involvement of 11q23 and changes in immunophenotype. 217 64

Hairy cell leukemia (HCL) cells are B lymphocytes expressing monoclonal surface bound immunoglobulins, B cell specific antigens, and activation markers. Based on immunophenotyping analysis, HCL cells have been reported to express simultaneously multiple Ig heavy chain isotypes. This is in contrast with the majority of other B cell malignancies. To analyse the tumor cell Ig in more detail, we have prepared somatic cell hybridomas from two patients with HCL. In both cases we found that the tumor cell derived hybridomas secreted IgM, IgG, or IgA indicating that a class-switch event does occur within the monoclonal tumor cell population. However these hybridomas expressed only single isotypes. The clonal relatedness of the tumor-derived Ig was shown by Ig gene analysis and by reactivity with a panel of idiotype specific antibodies. The tumor Ig of one patient analysed showed a striking variability in idiotope expression, indicative of somatic mutations of the expressed Ig genes. To our knowledge this is the first example of HCL and of a B cell malignancy other than follicular lymphoma for which somatic mutations have been demonstrated. This finding might be important for the therapeutic approach based on monoclonal anti-idiotype antibodies.
Leukemia 1990 Dec
PMID:Isotype switch and idiotype variation in hairy cell leukemia. 224 8

Immunoglobulin heavy chain gene rearrangement serves as a marker of cell lineage and clonality in B lymphoproliferative disorders. We have used polymerase chain reaction (PCR) gene amplification to detect immunoglobulin gene rearrangements involving VH251, a heavy chain variable region preferentially utilized in B lymphoproliferative disorders. Using synthetic amplimers derived from VH251 and the heavy chain joining region, under conditions of high stringency, a homogeneous VH251-specific fragment of approximately 350 bp could be amplified from leukaemic DNA. Of 53 cases of B lineage acute lymphoblastic leukaemia screened for VH251 rearrangement by PCR, 10 were positive. A background level of VH251 rearrangement could also be amplified from normal peripheral blood and bone marrow DNA, but a VH251 rearranged leukaemic clone representing 0.01% of bone marrow mononuclear cells could be readily detected. The application of PCR to detect immunoglobulin gene rearrangement involving VH251 and potentially other preferentially utilized V regions provides a sensitive method both for tracking malignant B cells and for the study of normal B cell developmental pathways through which B lineage malignancies arise.
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PMID:Detection of immunoglobulin gene rearrangement in B lymphoid malignancies by polymerase chain reaction gene amplification. 233 34

In addition to conventional morphological, histological and immunological marker studies, cells from 150 children with leukemia or non Hodgkin's lymphoma were analysed using the Southern blot hybridization technique to examine immunoglobulin- (Ig) and T-cell receptor (TCR) gene rearrangements. Patients with B-lineage leukemia or NHL demonstrated in 90% an Ig heavy chain gene rearrangement, 6% with an additional light chain kappa gene rearrangement. Combined Ig- with TCR-beta-gene rearrangements were mainly found in patients with common ALL: 19% at first presentation, and 33% in relapse. Moreover, 6 c-ALL patients showed rearrangements in all 3 gene loci (JH-, Ck- and TCR). Based on the developmental hierarchy of Ig- and TCR gene rearrangements it was possible to further subclassify c-ALL into different stages of B cell development. No correlation could be established between the different constellations of gene rearrangements, the number of rearranged fragments and the course of illness. All patients with T-lineage leukemia or NHL demonstrated TCR rearrangements of the beta-, g- and delta-gene loci, two with an additional Ig gene rearrangement. These data confirm recent reports indicating that immunoglobulin heavy chain gene rearrangements are not restricted to B-lineage neoplasms. Furthermore, non-germline configuration was found in tumor cells of every patient with AUL, O-ALL and AHL, permitting a classification to B- or T-cell lineage. Noteworthy is that every AML patient with Ig- and/or TCR gene rearrangements showed a poor or non-response towards therapy. Specimens of individual patients with differently involved tissues at diagnosis always showed an identical rearrangement. The intensity depended on the number of infiltrating blast cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical applications of the study of immunoglobulin and T-cell receptor gene rearrangements in acute leukemia and non-Hodgkin's lymphoma in children]. 239 11


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