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

The pattern of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements was determined in 87 patients with acute and chronic leukaemias and myelodysplastic syndromes by Southern blot hybridisation. All 31 cases of common, B cell and null cell acute lymphoblastic leukaemia, and B cell chronic lymphocytic leukaemia showed Ig heavy chain (JH) rearrangement, and TCR (beta-chain) rearrangement was seen in all 5 cases of T cell acute lymphoblastic leukaemia. Inappropriate JH and TCR (beta) rearrangements were present in some cases of T-ALL (60%) and common acute lymphoblastic leukaemia (18%), respectively. For the 19 patients with acute leukaemias following chronic myeloid leukaemia, blastic transformation, all 4 with lymphoid transformation and 3 of the 15 with myeloid transformation had JH rearrangement, and 3 CD10-positive lymphoid transformation and 2 myeloid transformation had their TCR (beta) genes rearranged. In conclusion, the pattern of Ig and TCR gene rearrangements correlated well with the cell lineage. However, cross-lineage rearrangements were more commonly seen in patients with acute leukaemias following chronic myeloid leukaemia blastic transformation, as compared to the de novo cases.
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PMID:Rearrangement of immunoglobulin and T cell receptor genes in acute and chronic leukaemias. 185 Sep 43

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

To identify the biological characteristics of so called stem cell leukemia (SCL), of which leukemic blast cells should be derived from pluripotent stem cells, immunophenotypical and genotypical analysis and response to several hematopoietic cytokines were studied in 272 cases with acute de novo leukemia. In 132 cases with acute myelogenous leukemia (AML), some cases of CD19+ and/or CD7+ AML were considered as SCL. In cases with myeloperoxidase negative acute lymphoblastic leukemia (ALL), cases of CD7 + CD1 - CD3 - CD4 - CD8 - My-Ag (myeloid antigens) +ALL, considered as those of T-precursor ALLs, and cases of HLA-DR + CD19 + CD20 - My-Ag + ALL, considered as those of B-precursor ALLs, were though to be SCL. We did not think the cases of ALL with dual genotype to be SCL, since dual genotype could not be considered as sings of ability to differentiate to multilineage but as products of the process of active V-DJ rearrangements of Ig heavy chain gene.
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PMID:[Diagnosis of stem cell leukemias in view of phenotypic and genotypic analysis]. 189 Jul 37

The authors investigated cytoplasmic immunoglobulins of the leukemic cells from 20 adult cases with non-T-cell acute lymphocytic leukemia (ALL) and from three cases with chronic myelogenous leukemia in lymphoid blast crisis using immunoelectron microscopy. They also studied these cases using various monoclonal antibodies. Of the 23 examined cases, nine were negative for both heavy and light chains of immunoglobulins; the authors defined these as common ALL. Two cases were positive for the mu chain but were negative for light chains; the authors defined these as pre-B-cell ALL. The remaining 12 cases were positive for either kappa or lambda light chains; these were defined as B-cell ALL. Of the 12 cases positive for light chains, 11 were positive for the lambda chain. Seven cases of the 11 positive cases for the lambda chain were negative for heavy chains. Eleven cases were positive either for both My4 and My9 or for one of the two antibodies. From these results, the authors conclude the following: (1) the ratio of pre-B-cell ALL among non-T-cell ALL cases (two of 23 cases) was lower in adults than in children; (2) of the light chain-positive cases, the lambda light chain-positive cases predominated (11 of 12 cases); (3) heavy chain-negative, lambda chain-positive cases (seven cases) were observed; and (4) one half of the leukemia cases showed dual phenotypes of B-cell and myeloid cell lineages.
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PMID:Predominant expression of lambda light chain in adult cases with non-T-cell acute lymphocytic and chronic myelogenous leukemia in lymphoid blast crisis. 190 73

Sixty precursor B-cell acute lymphoblastic leukemia (ALL) patients were analyzed for the configuration of their immunoglobulin (Ig) genes. Rearrangements and/or deletions of the Ig heavy chain (IgH), Ig kappa chain (Ig kappa), and Ig lambda chain (Ig lambda) genes were detected in 98, 48, and 23% of cases, respectively. Although these percentages suggest the presence of a hierarchical order in IgH and Ig light chain (IgL) gene rearrangements during B-cell differentiation, no correlation was found between the immunophenotype of the precursor B-ALL and the arrangement patterns of their IgH and IgL genes. Multiple rearranged IgH gene bands, generally differing in density, were found in 27 (45%) of the precursor B-ALL in various restriction enzyme digests. Cytogenetic data were used to determine whether the presence of more than two rearranged IgH gene bands was caused by hyperdiploidy of chromosome 14 or other chromosome 14 aberrations. The combined cytogenetic and IgH gene data allowed the precursor B-ALL to be divided into three groups: a monoclonal group (n = 36; 60%), a biclonal group (n = 16; 27%), and an oligoclonal group (n = 8; 13%). In five biclonal ALL biclonality at the Ig kappa gene level was also found. Such subclone formation was not detected at the Ig lambda gene level. As the detection limit of the Southern blot technique is 2-5%, it might well be that small subclones remained undetected, implying that the frequency of subclone formation at the IgH gene level in precursor B-ALL is probably higher than 40%. It has been suggested that precursor B-ALL with multiple IgH gene rearrangements have a higher tendency to relapse. Although higher relapse rates were found in the oligoclonal group (53%) and in the combined bi-oligoclonal group (33%) compared with the monoclonal group (20%), the log rank trend test showed no significance. The occurrence of multiple subclones in precursor B-ALL as found by IgH gene analyses will severely hamper the detection of minimal residual disease using the polymerase chain reaction (PCR) mediated amplification of 'tumor-specific' IgH gene junctional regions, because it cannot be predicted which detectable (or undetectable) subclone will cause minimal residual disease and/or relapse. Therefore it can be expected that the PCR technique will frequently produce false negative results during the follow-up of precursor B-ALL.
Leukemia 1991 Aug
PMID:Multiple rearranged immunoglobulin genes in childhood acute lymphoblastic leukemia of precursor B-cell origin. 190 9

Wild-type p53 protein is a growth modulator whose inactivation has been found to be a key event in malignant transformation. Reconstitution of wild-type p53 in the p53-nonproducer, Abelson murine leukemia virus-transformed pre-B-cell line L12 gave rise to stably growing clones. Wild-type p53-producer derived cell lines exhibit an altered cell cycle, however. More cells with an extended G0/G1 phase were found than in the p53-nonproducer parental cell line. Furthermore, when injected into syngeneic mice, these cells induced a lower incidence of tumors and these tumors were less aggressive. Analysis of immunoglobulin expression revealed that wild-type p53 induced the expression of cytoplasmic immunoglobulin mu heavy chain. In addition, these derived cells lines exhibited increased levels of a B-cell-specific surface marker, B220. These results suggest that wild-type p53 may function as a cell differentiation factor that can induce development of pre-B cells into a more advanced stage in the pathway of B-cell maturation. In these pre-B cells, wild-type p53 may induce cell differentiation without terminal growth arrest of the cell population.
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PMID:Involvement of wild-type p53 in pre-B-cell differentiation in vitro. 192 60

Polymerase chain reaction (PCR) was used to amplify the DNA fragments of the complementarity determining region 3 of the immunoglobulin (Ig) gene heavy chain from the leukemic cell specimens of patients with acute and chronic lymphoid leukemias of B-cell lineage. Two different pairs of primers were tested. Fourteen of the 17 (82%) cases of acute lymphoblastic leukemia (ALL), and all 15 cases (100%) of B-cell chronic lymphocytic leukemia, who had rearrangement of the Ig gene heavy chain by Southern analysis, were positive by PCR with either one or both pairs of primers. This technique was able to detect leukemic cells at the level of 0.1%. Applying it to study the remission marrow specimens following induction chemotherapy was more useful than morphology alone in predicting early relapse of the leukemia.
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PMID:Detection of immunoglobulin gene rearrangement in acute and chronic lymphoid leukemias of B-cell lineage by polymerase chain reaction gene amplification. 195 17

Bone marrow samples of 16 patients (two adults and 14 children) with a B lineage acute lymphoblastic leukaemia (ALL), and in whom Ig heavy chain gene rearrangements were detectable at diagnosis using polymerase chain reaction (PCR), were studied during evolution using PCR. The VDJ junctional fragment of the Ig heavy chain rearranged gene was amplified at diagnosis. After length reduction by restriction digestion, the amplified fragment was recovered by chromatography, labelled using a specific hexamer as a primer and directly used as a clonospecific probe. The sensitivity of the PCR ranged from 1:10(4) to 1:10(5) cells, depending on the patient's rearrangement. Residual disease (MRD) was detected in most of the patients achieving a complete remission after induction therapy, regardless of the long-term outcome of treatment. However, in patients remaining in complete remission, the level of MRD showed a tendency to decrease and ultimately become undetectable for variable periods of time, while in patients eventually relapsing there was a trend for MRD to persist at stable levels and even to increase before relapse was clinically evident. We conclude that the use of a simplified methodology for obtaining a clonospecific probe from the Ig heavy chain gene, though less sensitive than the sequencing methodology, is a valuable and readily available tool to monitor MRD in a high proportion of B lineage ALL.
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PMID:Follow-up of residual disease (MRD) in B lineage acute leukaemias using a simplified PCR strategy: evolution of MRD rather than its detection is correlated with clinical outcome. 195 77

Acute lymphoblastic leukaemia (ALL) of B-cell lineage typically arises as a monoclonal expansion of committed B-lymphocyte precursors that are arrested at an immature stage of differentiation. From Southern hybridization analysis of immunoglobulin heavy chain (IgH) genes in leukaemic blasts, the occurrence of a sizeable minority of patients displaying multiple (greater than two) rearranged heavy chain alleles has been widely reported. In at least some patients these data are consistent with the presence of oligoclonal populations of precursor B-cells. We have used a more sensitive, polymerase chain reaction based immunoglobulin gene 'fingerprinting' approach in the analysis of B-cell clonality in eight patients with common ALL which were apparently monoclonal on the basis of Southern blot analysis of their IgH genes. The results revealed an oligoclonal pattern of IgH gene rearrangement in half of the patients analysed, implying that oligoclonality at the level of B-cell commitment, as defined by IgH gene rearrangement, is much more widespread in this disease than has previously been recognized.
Leukemia 1991 Oct
PMID:Immunoglobulin heavy chain gene fingerprinting reveals widespread oligoclonality in B-lineage acute lymphoblastic leukaemia. 196 Oct 17

A patient with chronic lymphocytic leukemia (CLL) transforming into a small non-cleaved cell lymphoma (SNCL) with the occurrence of a t(8;22) is described. The SNCL and the CLL were both found to have a germline lambda light chain gene configuration and the same heavy chain and kappa light chain gene rearrangements. The SNCL was CD10 (CALLA) negative and appeared to be CD5 negative. It is concluded that the SNCL is derived from the CLL and that activation of the c-myc oncogene may have played a role in this transformation.
Leukemia 1991 Nov
PMID:Transformation of chronic lymphocytic leukemia to small non-cleaved cell lymphoma: a cytogenetic, immunological, and molecular study. 196 Oct 39


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