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

Rearrangement of the immunoglobulin heavy chain (IgH) gene is widely exploited as a marker of B cell lineage and clonality in the pathology of lymphoproliferative disorders. We have developed a simple, polymerase chain reaction (PCR) based method for detecting IgH gene rearrangement which relies on the observation that by using a panel of PCR amplimers specific for each of the six heavy chain variable region families in conjunction with a common joining region amplimer, clonal rearrangement can be detected in over 90% of cases of B lymphoid malignancy. By using radiolabelled amplimers and exploiting the size heterogeneity resulting from independent IgH rearrangement events, we show that high resolution gel electrophoresis can be used to generate a 'fingerprint' representing the spectrum of B cell clonality in complex populations of B lymphocytes. The method effectively scans the entire IgH gene rearrangement repertoire and is capable of detecting rare clonal or oligoclonal B lymphoid cell populations. In normal bone marrow mononuclear cells, clonal IgH rearrangement could be readily detected at a sensitivity of 10(-3). We illustrate the application of the method in assessing the spectrum of B cell clonality occurring in an autoimmune condition. Hashimoto's thyroiditis, and in a malignant B cell disorder, chronic lymphocytic leukaemia. In addition, we explore the potential application of the technique in tracking minimal residual disease and for monitoring clonal evolution in acute lymphoblastic leukaemia.
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PMID:Immunoglobulin gene 'fingerprinting': an approach to analysis of B lymphoid clonality in lymphoproliferative disorders. 201 50

Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.
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PMID:[Acute unclassified leukemia with bone marrow necrosis]. 202 Jan 20

A cell line, designated HAL-01, was established from the blood cells of a patient with acute lymphoblastic leukemia (ALL) with a myeloid-associated marker. Both the cell line and the patient's fresh leukemia cells had the chromosomal translocation t(17;19)(q21;p13). Morphologically and cytochemically, the cells were lymphoid in appearance. Immunophenotyping of the donor's leukemia cells revealed that they express B lineage antigens (CD10+, CD19+, CD20+, CD22+); the myeloid-associated antigen (CD13) detected in the donor's leukemia cells was not expressed by the established cell line. The HAL-01 cells have a rearrangement of the immunoglobulin heavy chain gene, while the T-cell receptor beta-chain genes remain in the germline configuration. The gene encoding the binding proteins for the kappa-light chain enhancer (kappa E2), which is involved in pre-B-ALL cells with the t(1;19) (q23;p13) translocation, is not rearranged in the cell line. The HAL-01 cells were transplantable into the peritoneum of untreated nude mice where they grew as an ascites tumor. The growing tumor cells also infiltrated lymph nodes, liver, spleen, kidney, and bone marrow without exhibiting a particular change in the morphology of the neoplastic cells. Clonogenic assay in methylcellulose culture demonstrated that the proliferation of the HAL-01 cells was suppressed by interleukin-3 (IL-3) in a dose-dependent fashion, with maximum inhibition occurring at concentrations greater than 100 U/ml. Treatment with IL-3 reduced the number of viable cells as well as induced morphological changes without concomitant changes in cytochemical reactions or immunophenotypic expression. Reduction of 3H-thymidine incorporation by exposure of IL-3 was blocked by the pretreatment of neutralizing anti-IL-3 antibody, but not by neutralizing anti-TGF-beta antibody. Thus, HAL-01 is a unique ALL cell line exhibiting proliferative suppression by IL-3 that may prove useful in studying the interactions of cytokines in ALL.
Leukemia 1991 Apr
PMID:Establishment of a novel heterotransplantable acute lymphoblastic leukemia cell line with a t(17;19) chromosomal translocation the growth of which is inhibited by interleukin-3. 202 99

Molecular analysis and blast colony assay were performed on patients with Philadelphia chromosome-positive acute leukemia (Ph+ AL). All patients were diagnosed as ALL- L2 and 3 were My+ ALL. Nine of the 12 cases had rearranged immunoglobulin heavy chain, and 4 had rearranged TCR beta. TCR gamma rearrangement was noted in 3 patients, and TCR delta involvement was also noted in 6 patients. Clonal culture analysis revealed that leukemia cells of M-BCR rearranged Ph+ AL cases had a potential to proliferate by myelopoietic CSFs and ILs, however, M-BCR nonrearranged Ph+ AL did not. These results indicate biological and immunogenotypic heterogeneity of Ph+ AL.
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PMID:[Immunogenotypic and clonal culture studies in Philadelphia chromosome-positive acute leukemia]. 206 75

We report here a cytogenetic and molecular analysis of two cases of T-cell leukemia with t(14;14) (q11.2;q32). Through in situ hybridization and Southern blotting, using radioactively labeled immunoglobulin heavy chain (IGH) and alpha T-cell receptor (TCRA) gene probes, we found in both tumors that the loci of both IGH and TCRA were rearranged. Molecular analysis of the t(14;14) clearly demonstrated that in some tumors rearrangements of the IGH and TCRA genes are associated with interchromosomal exchanges that result in specific chromosome translocations that confer a proliferative advantage and predisposition to leukemic transformation. The implication of these rearrangements for normal and neoplastic T-cell development is discussed.
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PMID:Immunoglobulin heavy chain and alpha T-cell receptor genes rearrange in T-cell leukemia associated with a t(14;14) (q11.2;q32) translocation. 211 59

We describe the haematological findings and clinical course of a 15-year-old male who presented with a spontaneous acute lymphoblastic leukaemia. The lymphoid origin of the leukaemia was supported by cell surface antigen studies and immunoglobulin heavy chain gene analysis. Bone marrow karyotype was simple monosomy 7 and the lymphoblasts expressing the myeloid associated antigen CD 33. Both of these features have been previously shown to indicate a poor prognosis. The findings in this patient support a previous hypothesis that monosomy 7 can arise at the stem cell level.
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PMID:Monosomy 7, leukaemia and immunoglobulin heavy chain gene rearrangement. 211 32

To develop a sensitive and specific assay for minimal residual disease in acute lymphoblastic leukemia (ALL), we exploited the enormous diversity of genomic sequences created by immune receptor gene rearrangements. To isolate clone-specific sequences, we first synthesized oligonucleotides that match conserved variable (VH) and joining (JH) sequences flanking the third hypervariable region (HVR3) in the rearranged immunoglobulin heavy chain (IgH) locus. In polymerase chain reactions (PCR), these primers were then used to amplify the intervening HVR3 segments from leukemic DNA samples. Of 12 B-lineage ALLs studied, ten generated one or more fragments of the size expected for HVR3 gene segments. Thus, this single pair of amplimers was sufficient to isolate HVR3 sequences from a majority of acute lymphoblastic leukemias. To verify that the amplified fragments originated from HVR3 alleles and to assess their diversity, we sequenced 7 PCR products derived from 6 leukemias. In addition to elements of recognized D segments, each of the 7 fragments contained novel VH-D and D-JH junctional sequences, including N nucleotides, not known to be present in the germline. Each sequence was unique, and allele-specific oligonucleotide probes hybridized only to HVR3 segments from which the probes were derived. Therefore, as anticipated, these HVR3 segments appeared to possess the diversity required to serve as clonal markers for leukemic populations. To demonstrate that these amplified HVR3 alleles could serve as the basis for a sensitive and specific assay to detect rare leukemic cells, we analyzed in detail one pre-B leukemia that had rearranged 2 IgH alleles. The HVR3 sequences were shown to be linked to rearranged JH-containing restriction fragments in digests of genomic DNA, establishing their origin in the leukemic cells. We synthesized oligonucleotides corresponding to the unique junctional sequences in the HVR3 segments. Using these novel amplimers in an allele-specific amplification and hybridization procedure, we showed that this assay can detect 10 leukemic cells in a background of 10(6) normal blood mononuclear cells. In contrast, the leukemic HVR3 sequences were not detected in extracts of normal or unrelated remission leukemic leukocytes. We conclude that the assay for specific IgH HVR3 sequences is a realistic strategy for detection of minimal residual disease in B-lineage ALL.
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PMID:Detection of minimal residual disease in acute lymphoblastic leukemia using immunoglobulin hypervariable region specific oligonucleotide probes. 212 20

Dimethyl-sulphoxide-induced Friend leukaemia erythroblasts (IFLE) which had been damaged by treatment with inhibitors of protein synthesis (cycloheximide, puromycin) were incubated with normal mouse serum or with doubling dilutions of it. The erythroblasts were subsequently tested for their binding of natural antibodies of all the major immunoglobulin (Ig) isotypes and both light-chain types, using Fc- and light-chain-specific FITC-immunoconjugates, and flow cytometry. After short-term (4-h) exposure of IFLE to puromycin, some binding of IgG but not of IgM or IgA could be demonstrated. By contrast, prolonged (17-h) exposure of IFLE to cycloheximide or puromycin resulted in their reaction with antibodies of all major isotypes (IgM, IgG1, IgG2a, IgG2b, IgG3, IgA) containing kappa-light chains. Under these conditions of damage the percentage of IgM- or IgG-binding IFLE significantly exceeded that of IgA-reactive cells. Moreover, the percentage of damaged IFLE which bound IgG2a or IgG3 was greater than that of cells which bound IgG1 or IgG2b. The percentage of damaged IFLE which bound a certain Ig-isotype did not correlate with the concentration of that Ig-isotype in normal mouse serum. The results suggest that natural antibodies of all major isotypes containing kappa-light chains bind specifically to severely damaged IFLE and could facilitate their interaction with macrophages in a concerted manner.
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PMID:Natural serum antibodies which bind to damaged erythroblasts: isotypes and light-chain composition. 212 88

T cell receptor delta (TCR) genes have been recently identified as rearranging during the early stages of T cell differentiation. We have analyzed the configuration of these genes in 47 unselected acute nonlymphoid leukemias. Morphology, phenotype, immunoglobulin heavy chain, and T cell receptor beta and gamma chain gene configuration were also studied. We have documented TCR delta gene rearrangements or deletions in eight cases using a genomic J delta 1 probe. The comparison of morphological, phenotypical, and molecular findings from these cases with those from control acute myeloid leukemias whose TCR delta genes were in germline configuration show that TCR delta rearrangements occur predominantly in immature leukemia exhibiting extensive lineage infidelity. The most striking feature was the frequent expression of the CD10 antigen. These data show that inappropriate gene rearrangements occur nonrandomly in myeloid leukemias and suggest that common mechanisms may be involved in the regulation of gene rearrangements and in the expression of some differentiation antigens.
Leukemia 1990 Feb
PMID:T cell receptor delta gene rearrangements occur predominantly in immature myeloid leukemias exhibiting lineage promiscuity. 213 46

We have investigated the interaction of mouse (m) IgE with its Fc epsilon RI on rat basophilic leukemia cells using a set of chimeric Ig that were constructed by exchanging homologous H chain C domains between human (hu) IgG1 and mIgE. Binding affinities were examined with equilibrium and kinetic measurements, and we found that epsilon/C gamma 3 (mIgE with C epsilon 4 replaced by C gamma 3) was indistinguishable from mIgE. The huIgG1 and the other chimeric Ig, which did not contain both C epsilon 2 and C epsilon 3, did not bind detectably to rat basophilic leukemia cells (Ka less than 10(6) M-1). The ability of these chimeric Ig to stimulate a cellular response (degranulation) in the presence of multivalent Ag was also tested. The epsilon/C gamma 3 was indistinguishable from mIgE in eliciting a high level of degranulation, whereas the other chimeric Ig stimulated no response even when they were preaggregated to enhance their binding avidity. These results demonstrate that C epsilon 4 may be replaced by C gamma 3 without affecting the binding and cell activating properties of mIgE. The lack of binding by the other chimeric Ig indicates that both C epsilon 2 and C epsilon 3 are necessary for the binding interaction.
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PMID:Mapping the site of interaction between murine IgE and its high affinity receptor with chimeric Ig. 214 5


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