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

It has been shown that a 600 bp long cluster of cell lineage specific hypomethylated sites in the major breakpoint cluster region (M-bcr) on chromosome 22 exists in hematopoietic cells. To determine possible relationships between methylation patterns within the M-bcr and the stage of hematopoietic cell development, the M-bcr methylation status of 39 patients with leukemia and lymphoma and two patients with myelodysplastic syndrome with non-rearranged M-bcrs was examined by BgIII-HpaII digestion. In the myeloid malignancies, the presence of a hypermethylated 4.8 kb BgIII-BgIII M-bcr allele was directly proportional to the combined myeloblast and promyelocyte percentage of the specimen, whereas the presence of a 2.5 kb BgIII-HpaII allele was directly proportional to the combined percentage of monocytic cells and neutrophils. All five acute monoblastic leukemias showed a methylation pattern that closely resembled neutrophils. All of thirteen surface immunoglobulin positive B-cell malignancies showed a distinct methylation pattern consisting of three or more BgIII-HpaII restriction fragments of 2.5 kb or less in length. The B-cell precursor leukemias showed heterogeneous M-bcr methylation patterns, with four of seven showing a B-cell pattern and three showing a hypermethylated pattern with 4.8, 3.1/3.0 and/or 2.5 kb BgIII-HpaII M-bcr alleles. It is concluded that the M-bcr methylation status is related to the maturation of the neutrophil series; the surface immunoglobulin positive B-cell malignancies are characterized by a distinct, extreme hypomethylation pattern of the M-bcr; and the B-cell precursor malignancies appear to have a heterogeneous M-bcr methylation pattern.
Leukemia 1992 Jan
PMID:Methylation status of the major breakpoint cluster region in Philadelphia chromosome negative leukemias. 134 43

In chronic myelogenous leukemia (CML) malignant cells are characterised by the Philadelphia chromosome (Ph), resulting from a translocation t(9;22). The position of the breakpoint within the major breakpoint cluster region (M-bcr) on chromosome 22 has been shown to correlate with the clinical course of the disease or, more recently, thrombopoietic activity. We have therefore determined the breakpoint localisation in 53 Ph-positive CML patients. Following the 5'/3'-region definition of Inokuchi et al. Leukemia Research 15, 1067 (1991) [1], 22 of our patients have 5' and 31 of our patients have 3' orientated breaks. No correlation was found between platelet counts and breakpoint localisation.
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PMID:No correlation between site of breakpoint in the BCR gene and platelet counts in Philadelphia chromosome-positive CML. 140 23

The paper describes a case of Philadelphia (Ph) positive acute lymphoblastic leukaemia (ALL) presenting with high white cell count and central nervous system involvement. Immunophenotypically the case was characterized as common ALL. The t(9;22) abnormality corresponded to a rearrangement within the breakpoint cluster region gene, while antigen receptor gene studies showed multiple rearrangements of the immunoglobulin heavy chain gene (IGH) concomitant with a single rearrangement of the T cell receptor beta chain gene (TCR beta). We speculate that this case represents the neoplastic transformation of a stem cell, the Ph abnormality being involved in the early steps of transformation. It is conceivable that the IGH but not the TCR beta gene was accessible to recombination within the malignant clone, thus generating the multiple rearrangements observed. If this is the case, these findings would appear to be compatible with the hypothesis that antigen receptor gene rearrangements may be partly dependent on the accessibility of the corresponding genetic loci.
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PMID:A complex pattern of antigen receptor gene rearrangements in a case of Philadelphia positive acute lymphoblastic leukaemia. 140 37

Immunogenotypic changes in 32 patients with B-precursor acute lymphoblastic leukemia (ALL), including three patients with t(4;11) and 13 with t(9;22), were determined using immunoglobulin heavy (IgH) chain gene probe and T-cell receptor beta, gamma and delta chain gene probes. Clonogenic assay was performed in 12 of the 32 patients. In this study, four patients had a germline configuration of the IgH chain gene, showing a dissociation between phenotypic and genotypic expression; three patients had Philadelphia-positive (Ph+) ALL. The immunogenotypic manifestation in Ph+ ALL does not depend on whether the leukemia cells had rearrangement within the major breakpoint cluster region (major-BCR) DNA sequence or the leukemia cells had myeloid-associated antigens. Colony assay using various recombinant cytokines demonstrated that the leukemia cells from four of 12 patients formed colonies in response to myelopoietic stimulants; three of the four patients were major-BCR-rearranged Ph+ ALL. Notably, cells from one patient with Ph+ ALL formed colonies on the addition of granulocytic colony-stimulating factor. This indicates not only the biological heterogeneity of ALL cells but also that some of the characteristics of the cells are related to specific chromosome changes.
Leukemia 1992 Apr
PMID:Immunogenotypes and clonal culture analysis in B-precursor acute lymphoblastic leukemia. 158 87

The breakpoints in chromosome 22 were determined in five children with Philadelphia-positive chronic myeloid leukemia. All had rearrangements within the major breakpoint cluster region (M-bcr). Four patients had breakpoints in the 5' region of M-bcr (zones 1-3), whereas one had a rearrangement in the 3' region (zone 4). The patient with the 3' rearrangement was the only one to develop a lymphoid blast crisis; he also had a substantially longer survival (102 months) than the others (11-54 months).
Leukemia 1992 Jul
PMID:Molecular analysis of Philadelphia-positive childhood chronic myeloid leukemia. 162 93

We have studied phenotypic and clinical features in a consecutive series of 45 patients with chronic myelogenous leukaemia (CML) in blast crisis (BC). In addition, in 22 of these patients we have analysed the genotypic characteristics including immunoglobulin, T-cell receptor (TCR) and major breakpoint cluster region (M-bcr) gene organization. The granulomonocytic and megakaryoblastic lineages are the most commonly involved in these BC of CML (33% and 33% of cases, respectively); only 18% of our cases displayed a lymphoid phenotype. Moreover, both morphological and immunophenotypic studies revealed the frequent coexistence of two or three cell populations, especially when the megakaryoblast component is involved. The lymphoid BC displayed the highest incidence of complete remissions although this was not associated with a longer survival. Only minor differences between the different myeloid subgroups were observed. Immunoglobulin heavy chain (IgH) gene rearrangement was found in five of the six lymphoid BC and in one myeloid BC. Only one case showed k light chain gene rearrangement. In all but one myeloid BC the TCR-beta gene was in germline configuration. The TCR-gamma gene was rearranged in all lymphoid and one myeloid BC, while TCR-delta gene rearrangement was detected in 67% and 16% of the lymphoid and myeloid BC, respectively. Most of the lymphoid BC (4/5) had the M-bcr breakpoint in subregion 3, while the myeloid BC had the breakpoint either in subregion 2 or 3. No differences between the different myeloid phenotypic subgroups were observed in relation to breakpoint.
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PMID:Immunophenotypic, genomic and clinical characteristics of blast crisis of chronic myelogenous leukaemia. 175 68

The configuration of immunoglobulin (Ig) and T-cell receptor (TCR) genes was investigated in a case of atypical chronic myeloid leukemia (aCML) lacking a cytogenetically detectable Philadelphia chromosome and molecular evidence of breakpoint cluster region (bcr) rearrangement as determined by 5' and 3' bcr gene probes. Dual clonal rearrangement of Ig-heavy (H) and TCR-delta chain genes was identified. The genes for TCR-gamma and beta chain as well as Ig-kappa (k) chain were in germline configuration. These findings indicate transformation to have occurred in a hemopoietic stem cell with the capacity for antigen receptor gene rearrangement. The demonstration of cross-lineage rearrangement of both Ig and TCR genes lends support to evidence from G6PD alloenzyme studies that the target of transformation in aCML is an early stem cell not yet irreversibly committed to myeloid differentiation. Further studies are indicated to ascertain whether antigen receptor gene rearrangement constitutes a molecular marker useful in the diagnosis of aCML.
Leukemia 1991 Mar
PMID:Cross-lineage rearrangement of antigen receptor genes in atypical chronic myeloid leukemia. 182 35

The configuration of the T-cell receptor (TCR) beta, gamma and delta chain genes was analyzed in 16 cases of B-lymphoid blastic crisis of chronic myeloid leukemia (BC-CML) for a better definition of the biological aspects of this cellular population, in comparison with the molecular features of B-precursor acute lymphoblastic leukemia (ALL). All cases displayed B-phenotypic features, were Ph'-positive and had a rearranged configuration of the breakpoint cluster region (bcr) and of the immunoglobulin heavy chain gene region (JH). The TCR beta chain gene was rearranged in four cases (25%), all of which displayed a monoallelic rearrangement involving the J beta 2 region. The TCR gamma chain gene was rearranged in 13 cases (81%); 13 rearranged alleles utilized the J1/2 regions, while the remaining five utilized JP1. The V regions of the group I were mostly involved. The TCR delta chain gene was rearranged or deleted in 15 cases (94%); the 10 rearranged chromosomes displayed exclusively two patterns referable to partial recombinations, a V2-(D)-D3 and a (D)-D3 type. These two configurations are predominant in B-precursor ALL (75% of rearranged chromosomes) and almost absent in T-ALL. Taken together, these results document the close similarities between the genotypic features of B-lymphoid BC-CML and B-precursor ALL, not only in terms of the incidence of rearrangement but more relevantly with regard to the choice of regions involved in the recombinations. This aspect is particularly evident at the TCR delta locus level.
Leukemia 1991 May
PMID:Identical utilization of T-cell receptor gene regions in B-lymphoid blast crisis of chronic myeloid leukemia and B-precursor acute lymphoblastic leukemia. 182 53

We studied the nature of blast cells in 41 patients with acute leukemia following a previous primary myelodysplastic syndrome (MDS) by a combined multiparameter analysis including morphologic, immunophenotypic, and molecular genetic (Igs, T-cell receptor (TCR)-beta, -gamma, and -delta and the major breakpoint cluster region [M-bcr]) investigations. In addition, the clinical and hematologic characteristics according to the immunophenotype of blast cells were analyzed. Our results show that, although the granulocytic and/or monocytic lineages are those most commonly involved in these acute leukemias, other cell components, including the megakaryocytic and lymphoid, may be present (12% and 15% of the cases, respectively). Moreover, both morphologic and phenotypic studies show the frequent coexistence of two or three cell populations. Interestingly, in all cases the lymphoblastic component constantly displayed an early B phenotype (CD19+, CD10-, TdT+). Upon analyzing whether the type of MDS conditioned any differences in the immunophenotype of blast cells, we observed that, although the lymphoid lineage may be involved in all MDS subgroups, some differences emerge within the myeloid leukemic transformations. Thus, the refractory anemias with excess of blasts (RAEB) and RAEB in transformation displayed a significantly higher incidence of myeloblastic and megakaryoblastic transformations, while in the RA, RA with ring sideroblasts and chronic myelomonocytic leukemia, the granulo-monocytic phenotype predominated. In addition, our results show that the clinical and hematologic characteristics of these patients may be partially related to the immunophenotype of the blast cells. Ig heavy chain gene rearrangements were found in two of 19 patients analyzed (11%), one with a hybrid leukemia (lymphoid-myeloid) and the other with a granulo-monocytic phenotype. Two other hybrid transformations analyzed were in germline configuration. Gamma and delta gene rearrangements were found in 21% and 37% of these acute transformation, respectively. The TCR-beta and M-bcr were in germline configuration in all 19 cases studied. In summary, immunophenotype and molecular studies point to a pluripotent stem cell with preferential myeloid commitment as the target cell of leukemias following a primary MDS.
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PMID:Acute leukemia after a primary myelodysplastic syndrome: immunophenotypic, genotypic, and clinical characteristics. 146 36

A female patient with precursor B-cell acute lymphoblastic leukemia (precursor B-ALL) was analyzed cytogenetically. Karyotyping of the leukemic cells showed a Philadelphia chromosome (Ph1), and also showed a translocation between 2p13 and 14q32, which is thought to be specific for children with B-cell chronic lymphocytic leukemia. DNA analysis with both conventional and pulsed-field gel electrophoresis revealed the rearrangement of the c-abl gene, the BCR gene outside the 5.8 kb breakpoint cluster region (bcr or M-BCR), and the comigration of an abnormal Not I pHabl 5' and 3'-bcr fragment, indicating the presence of BCR/c-abl recombination. The JH gene was rearranged, but the JK gene showed a germline configuration, as with previously reported cases with a t(2;14). This case is the first report of a patient with Ph1-positive precursor B-ALL, in whom a specific translocation t(2;14)(p13;q32) is found simultaneously.
Leukemia 1991 Aug
PMID:Philadelphia chromosome positive precursor B-cell acute lymphoblastic leukemia with a translocation t(2;14)(p13;q32). 188 25


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