Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three cell populations with different DNA indices were demonstrated in a case of biphenotypic terminal transferase (TdT)/myeloid-positive acute leukemia which had developed from a pre-leukemic diploid population also expressing biphenotypic features. At the time of development of acute leukemia, flow-cytometric analysis revealed expression of TdT by the diploid, the tetraploid, and the near-triploid cells, but only the tetraploid cells carried the myeloid-specific M2 antigen. Cytogenetic analysis showed four stemlines, diploid, tetraploid, tetraploid with del(2), and near-triploid with del(2) and variable chromosome losses. In vitro treatment with retinoic acid induced the expression of the M2 antigen by the diploid cells as well. This in vitro result is consistent with a myeloid differentiation commitment of the pluripotent leukemic stem cell.
Leukemia 1989 Jan
PMID:Distinct antigen expression related to DNA ploidy in a case of biphenotypic leukemia. 290 10

A patient in complete remission from malignant melanoma but with refractory anemia after nitrosourea treatment developed acute biphenotypic leukemia. This disease, progression was accompanied by expansion of a cytogenetically abnormal clone. At first cytogenetic analysis, 1 year post discontinuation of chemotherapy, only 25% of the metaphases examined were hypodiploid with monosomy 7. Six months later, all of the metaphases seen were 45,XY,-7. Six months before overt acute leukemia was diagnosed, an additional chromosome abnormality emerged, t(2;3)(q31;q27). Although the translocation was present in all metaphases examined, the patient progressed into an acute leukemia with two components: one TdT-positive, Ia-positive, and the other TdT-negative, Ia-positive, monocytoid antigen-positive. This mixed leukemia was identified by double fluorescence staining for intranuclear TdT and surface labeling with a monocyte-specific monoclonal antibody.
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PMID:Biphenotypic leukemia with unusual chromosomal translocation in a patient treated for melanoma. 293 29

The cellular origin of acute undifferentiated leukemia (AUL) is still a matter of controversy. We report on two cases in which the diagnosis of AUL was established according to restricted criteria. Blast cells of both patients showed phenotypic conversion during the course of disease. In one case, within 24 days from starting treatment, the leukemic phenotype changed from AUL to acute myelomonocytic leukemia (FAB L1, TdT+ to FAB M4, TdT-). The initial phenotype of this acute leukemia was characterized by the co-expression of both B-lymphoid and myeloid markers on the same cell. Moreover, analysis of esterase isoenzyme pattern showed the whole spectrum of isoenzymes typically seen in myelomonocytic leukemias already at diagnosis, yet blast cells additionally contained all three isoenzymes of beta-hexosaminidase typically seen in AUL. However, examination of immunoglobulin (Ig) heavy chain gene rearrangement initially and after conversion revealed an identical monoclonal configuration of Ig heavy chain sequences in both samples. The second AUL patient relapsed after allogeneic bone marrow transplantation with common ALL-antigen (CALLA) positive acute leukemia. Subsequent Southern blot analysis showed a novel rearranged Ig fragment compared to the analysis before transplantation indicating that the leukemic clones prior to and after transplantation were not identical. No chromosomal abnormalities were observed in both cases. These data support the view that AUL cells originate from a pluripotent stem cell that is capable to differentiate in the myelomonocytic lineage (patient 1), and confirm the value of Ig gene analysis as marker for cellular clonality.
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PMID:Conversion of acute undifferentiated leukemia phenotypes: analysis of clonal development. 294 79

Chromosome studies in a case of T cell lymphoma/leukemia, in which a high proportion of the dividing cells had a t(8;14)(q24;q32) similar to that seen in Burkitt's lymphoma, are described. The tumor cells had a mature T cell phenotype (TdT-,CD3+,CD8+,CD4-) and were morphologically large granular lymphocytes and immunoblasts, both cell types with similar lysosomal granules in the cytoplasm. The immunoglobulin heavy chain gene and the T cell receptor beta chain gene were not rearranged, while the T cell receptor gamma chain gene was polyclonally rearranged. Mitoses were obtained only from spontaneously dividing cells in the absence of mitogens; 49 of the 50 metaphases analyzed were chromosomally abnormal and had a t(1;22)(q12;q13) and dup(1)(q31q32) in all of them; 48 metaphases had in addition a t(8;14)(q24;q32) which presumably arose during clonal evolution. The latter may be associated with the aggressive behavior of this T cell disorder by comparison with other proliferations of large granular lymphocytes. Although abnormalities involving 14q32 are characteristic of B cell disorders, they have also been described in T cell malignancies, suggesting that genes transcribed in T cells and/or oncogenic sequences significant in T cell neoplasia are present in 14q32.
Leukemia 1987 Dec
PMID:A t(8;14)(q24;q32) in a T-lymphoma/leukemia of CD8+ large granular lymphocytes. 296 53

The isoenzyme patterns of carboxylic esterase (E.C. 3.1.1.1) were studied in 74 proven human leukemia-lymphoma and 12 normal B-lymphoblastoid cell lines. These cell lines have been extensively phenotyped using poly- and monoclonal antibodies. Esterase isoenzymes were separated by isoelectric focusing and visualized by histo-cytochemical techniques. No leukemia-specific or (except for monocytes) blood cell type-specific isoenzyme or isoenzyme pattern could be detected. The monocytic element in some cell lines was characterized by a strong isoenzyme band which could be selectively and completely inhibited by sodium fluoride. The enzyme phenotypes were stably expressed in all subcultures of a given cell line and did not appear to have any cell cycle dependency. The leukemia-lymphoma cell lines have been subclassified into four major groups according to immunological parameters: T-cell, B-cell, myelomonocytic and non-T, non-B-cell. On the basis of immunological data the T-cell lines were assigned to five stages of differentiation. The number and staining intensity of the isoenzymes increased with differentiation of the T-cells paralleling the expression of immunological markers. The B-cell leukemia-lymphoma cell lines were divided into pre B-, B-, Burkitt lymphoma, multiple myeloma and hairy cell leukemia cell lines. Substantial variability among the isoenzyme patterns was detected ranging from immature profiles of pre B-cell lines to complete isoenzyme repertoires of multiple myeloma cell lines. No significant difference was seen between the isoenzymes of mature B-cell lines and normal B-lymphoblastoid cell lines. The most prominent feature seen in myelomonocytic cell lines was the monocytic band indicating a monocytic origin and separating the 'monocytoid' from the 'pure myeloid' cell lines. Considerable heterogeneity in the isoenzyme patterns was observed in the non-T, non-B cell groups which comprised erythroleukemia cell lines and cell lines arrested at a very early stage of lymphoid differentiation. These latter cell lines together with some T- and B-cell lines shared the common characteristics of positivity for cALLA, TdT and Ia antigens and an immature, incomplete isoenzyme profile. The results support the notions of maturation arrest and normal gene expression in leukemic cell populations. Furthermore, the importance of biochemical studies as part of the multiple marker analysis could be demonstrated.
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PMID:Isoenzyme studies in human leukemia-lymphoma cell lines--1. Carboxylic esterase. 298 79

The multidisciplinary approach of leukemia phenotyping, called multiple marker analysis, led to changes in the classification systems of normal hematopoiesis and leukemic cells, and introduced the use of a biological and functional definition of leukemia, rather than merely morphological-cytochemical descriptions. Two major conclusions can be drawn from the findings of multiple marker analysis: 1) differentiation of leukemia is not abnormal but blocked ("maturation arrest"), and leukemic cells retain normal maturation-linked markers; and 2) no leukemia specific marker could be detected so far. Although leukemic cells show general qualitative features in common with normal cells, some quantitative characteristics of these similar attributes are peculiar to leukemic blasts. Qualitative and quantitative enzymological characteristics help to identify the cell lineage involved and to determine the developmental point at which maturation arrest occurs. The expression of isoenzymes is often linked to the presumptive sequence of developmental stages. Subsets within ALL subtypes showed pronounced modifications in their isoenzyme patterns associated with increasing maturity. Thus, enzyme markers can provide refined definitions of subgroups by biochemical criteria. Based on recent observations using the enzyme markers TdT, adenosine deaminase, 5'-nucleotidase, purine nucleoside phosphorylase, acid phosphatase, and hexosaminidase, a scheme of enzymological expression in the various commonly accepted subtypes of acute lymphoid leukemia and acute nonlymphoid leukemia is presented. Enzyme marker analysis represents a useful tool as an adjunctive method in multiple marker analysis for assessing diagnosis, prognosis, and the evolutionary and pathogenetic mechanisms underlying the spectrum of leukemia subtypes. Furthermore, enzyme marker analysis may provide further insight into certain aspects of the pathobiology of leukemia which might not be elucidated by other methods.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Significance of enzyme markers as a part of multiple marker analysis in leukemia research. 300 Feb 10

Immunologic aspects of autologous bone marrow transplantation (ABMT), immunodiagnosis, patient monitoring, and the purging of bone marrow have been studied in individual patients. It was demonstrated that the most sensitive method for detecting lymphoid cells which show the phenotypes of ALLs of B or T lineage was double immunofluorescence staining for nuclear terminal transferase (TdT) and B or T lineage antigens. With the help of these sensitive tests in the presence of rabbit complement (C'), MAbs CD10 (RFAL3 of IgM class), CD19 (SB4 of IgM class), and their cocktail were capable of eliminating greater than 3 log blast cells of B lineage ALL in 84%, 75.5%, and 90% of cases, respectively. The same reagents lysed 26.8%, 0%, and 45% of blasts in the presence of human C'. CD7 (RFT2, IgG2) eliminated greater than 3 log T-ALL blast cells in 73% of cases. The proliferative fractions of leukemic blasts were also TdT+ and sensitive to lysis with MAb and C'. On the basis of these observations MABs were selected for purging in 36 patients undergoing ABMT in first remission (10 patients considered to be at a high risk of relapse), second and third remissions (23 and 2 patients), and without entering into remission (1 patient). The efficacy of eliminating the MAb-reactive cells from the bone marrow inoculum was also documented in five patients. By the use of sensitive immunologic assay (TdT/cytoplasmic CD3 double staining) in patients with T-ALL, no residual leukemia (less than 10(-4] could be detected at the time of transplantation. Following an observation period of 5-34 months, 24 of the 36 patients are alive and well with no procedure-related mortality.
Leukemia 1988 Aug
PMID:Autologous bone marrow transplantation in acute lymphoblastic leukemia--preclinical immunologic studies. 304 31

Bilineage differentiation along both the T lymphoid and the myeloid lineage while in in vivo diffusion chamber (DC) and in vitro suspension culture was observed in a case of acute unclassified leukemia (null-AL) and t(4;17). Prior to culture, the blast cells were TdT and la positive but did not express any lineage-specific antigenic markers. Furthermore, the immunoglobulin heavy chain and T cell receptor beta-chain genes were in germline configuration. Cytogenetically, all metaphases had the unique translocation t(4;17) (q25;q23) prior to and after culture, supporting the leukemic origin of the cells. During both DC culture and suspension culture with and without tetradecanoyl-phorbol-acetate (TPA), a substantial increase in the absolute and relative number of cells expressing both myeloid and T lymphoid antigenic markers occurred. Double-fluorescence analysis demonstrated the expression of antigenic markers of both lineages on the same population of cells, and electron microscopy revealed the induction of myeloperoxidase after both DC and suspension culture. Immunoglobulin heavy chain and T cell receptor beta-chain genes remained in germline configuration after treatment with TPA, when analyzed with JH and CT beta probes, respectively. These findings indicate that this case represents a null-AL with dual-lineage capabilities, which has probably arisen from the malignant transformation of a bipotential stem cell of lymphoid and myeloid progeny.
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PMID:Human acute unclassified leukemia with a unique t(4;17) chromosomal translocation expresses T lymphoid and myeloid surface antigens after in vitro culture. 309 22

A case of acute leukaemia with t(4;11) chromosomal abnormality in a 28-year-old woman is reported. At diagnosis, two blast cell populations were seen: 60% of the cells were small cells with lymphoid morphology, 40% were large cells with monocytic morphology. Cytochemical examination was consistent with acute myeloid leukaemia (peroxidase-positive in 10% of the cells), but surface markers were those of common acute lymphoblastic leukaemia (CALLA, B4, TdT-positive, but My7-, My9- and OKM1-negative). Five days after diagnosis, although the only treatment had been platelet transfusions, there was a change in morphological and immunological phenotype: 40% of the cells were lymphoid and 60% monocytic. Lymphoid markers were expressed in only 20-40% of cells, and myeloid markers appeared on up to 60% of cells. We conclude that t(4;11) leukaemia could originate in an undifferentiated progenitor cell, which can undergo further differentiation into lymphoblasts or monoblasts, and that we were able to observe this in vivo differentiation in our patient.
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PMID:Variations in morphological and immunological blast cell phenotype in a case of acute leukaemia with t(4;11) translocation. 310 60

In acute lymphoblastic leukemia (ALL) diagnostic samples and cell lines with unequivocal B cell precursor (common) or T cell precursor immunophenotypes, there is inappropriate or cross-lineage IgH or T cell receptor beta gene (TCR beta) rearrangement in approximately 25% of the cases. The frequency of such rearrangements is lower in mature lymphoid neoplasms and acute myeloblastic leukemia. The most immature B lineage ALL ('null' ALL) has a much lower frequency of TCR gene rearrangement than the common variant of B cell precursor ALL and also has a high frequency of oligoclonal rearrangements of IgH genes. Non-T leukemic cells with inappropriately rearranged TCR beta gene did not necessarily have a rearranged TCR gamma gene. Inappropriately rearranged IgH or TCR genes are usually not expressed at the mRNA level, and the gene for the TCR associated protein T3 delta is not detectably expressed at the mRNA or protein level in leukemias classified unambiguously as non-T. Five cases of acute leukemia with ambiguous or mixed lineage immunophenotypes (myeloid + T or myeloid + B) are described. These five had diverse patterns of IgH, TCR beta, and TCR gamma rearrangement, and all expressed terminal transferase concomitantly with MY9 (CD33). The T3 delta gene was expressed in two cases, which also expressed other T cell markers indicating that coordinated lymphoid lineage programs had been initiated. The implications of these observations for lineage-associated regulation of genes during normal differentiation and leukemogenesis are discussed.
Leukemia 1987 Sep
PMID:Lineage specificity of rearrangement and expression of genes encoding the T cell receptor-T3 complex and immunoglobulin heavy chain in leukemia. 311 13


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