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)

Two cases of T-cell chronic lymphoid leukaemia in adults were classified by recently developed immunological methods. Clinically there was splenomegaly, hepatomegaly, marked anaemia, para-aortic lymph nodes, cutaneous infiltration, little peripheral lymph-node enlargement and significant marrow infiltration. Immunological tests of membrane antigens revealed T-cell determinants. T-CLL may differ in its course and prognosis from B-CLL and may require different treatment.
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PMID:[T-cell leukaemia in adults: report of two cases (author's transl)]. 30 81

A five-year-old boy initially diagnosed common ALL was developed to acute myelomonocytic leukemia. At onset, the bone marrow was hypercellular and 77% of the cells were blasts, mainly lymphoblast-like cells and cytogenetic study demonstrated 45, XY, -7 in all blasts. Cytochemically most of those blasts were negative for peroxidase, sudan black B, alpha-NB esterase staining. The immunological phenotype was J5 (CD10)+, I2 (HLA-DR)+, SmIg-, CyIgmu-, Leu1 (CD5)-, OKT11 (CD2)-, MY7 (CD13)-, suggesting common ALL. Eight months later, the bone marrow cells were occupied with large sized blasts which were almost positive for peroxidase stain and the cells showed coexpression of Mo1 (CD11b)+, MY4 (CD14)+, MY7+, MY9 (CD33)+, MCS2 (CD13)+, I2+, J5-, B4 (CD19)-, Mo2 (CDw14)-, at relapse. He died 2 years and 6 months after his initial diagnosis. An autopsy was performed which revealed generalized infiltration of leukemic cells and aspergillosis of the lung. In general, monosomy 7 is associated with myelodysplastic syndrome in childhood, and is terminated to acute myeloblastic leukemia. In this case, bone marrow blasts demonstrated monosomy 7 cytogenetically, and this case was considered as an acute mixed lineage leukemia of bilineal type. And this case proved that a monosomy 7 can also be terminated to acute mixed lineage leukemia with both lymphoid and myeloid phenotypes.
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PMID:[An autopsy case of acute mixed lineage leukemia with monosomy 7 in a child]. 194 26

We determined the expression levels of the mdr1 and mdr3 multidrug-resistance genes (also known as PGY1 and PGY3, respectively) in peripheral blood cells from 69 adult patients with acute and chronic leukemias, using an RNase protection assay. Expression of mdr1 was found in samples from patients with acute nonlymphocytic leukemia (13 of 17), chronic myelocytic leukemia (CML, chronic phase, 10 of 10; blast crisis, three of four), acute lymphocytic leukemia (ALL, eight of 11), B-cell chronic lymphocytic leukemia (B-CLL, 17 of 17), hairy cell leukemia (HCL, one of two), and T-cell prolymphocytic leukemia (one of one), but not in B-cell prolymphocytic leukemia (B-PLL, 0 of seven). Expression of mdr3 was only detected in samples from B-cell lymphocytic leukemias: CML, lymphoid blast crisis (one of one), B-cell ALL (two of two), B-CLL (17 of 17), B-PLL (seven of seven), and HCL (two of two). In vitro drug uptake studies by on-line flow cytometry showed that in leukemia cells expressing either mdr1 or mdr3, the steady-state accumulation of daunorubicin could be significantly increased by addition of cyclosporine and, to a lesser extent, by verapamil. Because cyclosporine and verapamil are known as inhibitors of the mdr1-encoded P-glycoprotein drug-efflux pump, and because the mdr1 and mdr3 genes are highly homologous, our data suggest that the mdr3 gene encodes a functional drug pump in B-cell lymphocytic leukemias. The results of this study may have implications for clinical therapy for acute or chronic leukemias expressing the mdr1 or mdr3 gene, in particular, treatment with combinations of cytotoxic drugs plus agents that reverse multidrug resistance. Since mdr1 and mdr3 are frequently expressed in untreated as well as treated leukemia, such combination therapy should be considered for untreated patients as well as treated patients.
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PMID:Expression of mdr1 and mdr3 multidrug-resistance genes in human acute and chronic leukemias and association with stimulation of drug accumulation by cyclosporine. 197 61

We describe in vitro studies undertaken to characterize the expression of the proto-oncogene c-jun during differentiation of B-CLL cells. The phorbol ester TPA and the natural compound Bryostatin 1 (Bryo) were used to directly stimulate protein kinase C (PKC) while the calcium ionophone A23187 was employed to increase intracellular Ca2+. In quiescent cells c-jun mRNA expression was undetectable or at low levels. Upon treatment with TPA or Bryo, the steady-state levels of c-jun mRNA increased rapidly, reached a maximum at 0.5 or 1 hr, and then decreased in the B-CLL cells from all five patients analyzed; this reaction was augmented by the addition of A23187. Induction of c-jun mRNA by direct stimulation of PKC could be blocked by the PKC inhibitor H7. The present observations, along with other results on the induction of long-term phenotypical cellular changes, such as alteration of morphology and other features of differentiation, support the notion that the second messenger (via PKC) and the third messenger (via proto-oncogene products) pathways are intact in B-chronic lymphocytic leukemia cells.
Leukemia 1990 Jun
PMID:Expression of proto-oncogene c-jun during differentiation of B-chronic lymphocytic leukemia. 211 1

The neoplastic lymphoid cells in 33 patients with chronic lymphocytic leukemia (CLL), 1 case of prolymphocytic leukemia (PLL), and 29 patients with various types of non-Hodgkin's lymphoma (NHL) were examined for the expression of transferrin receptors (TR) using a panel of three anti-TR monoclonal antibodies (MAb). Both immunofluorescence and immunoperoxidase techniques were applied in each case. All cases of B-CLL (31) were negative for TR expression, while both the cases of T-CLL, and the only case of T-PLL showed significant TR-positive cell populations. Similarly, all 13 cases of "low-grade" NHL were TR negative, while 6 of 7 cases of "high-grade" lymphomas (lymphoblastic and immunoblastic) had up to 28% TR-positive cells. A proportion (4/9) of "intermediate grade" lymphomas had 10-15% TR positivity. Interestingly, the majority of B-leukemia/lymphoma (49/55) cases were TR negative, while all 8 cases of T-cell leukemia/lymphoma were TR positive. This clearcut association of TR expression with high-risk morphologic and immunophenotypic subgroups of lymphoid leukemia/lymphoma points to the potential role of TR as a prognostic marker in lymphoproliferative disorders.
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PMID:Correlation of transferrin receptor expression with histologic grade and immunophenotype in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. 218 55

Cytogenetic analysis was carried out in 28 B-CLL patients (21 males and 7 females, 38-85 years old, with median age 64 years, disease stage O-IV). Peripheral nominator cells (1 x 10(7)) or isolated B-lymphocytes were incubated in vitro for 5-7 days. The cells were stimulated by pokeweed mitogen (PWM), or phorbol myristate-acetate (PMA), with or without 10% conditioned medium (CM) derived from a T cell leukemia line or 10% B-cell growth factor (BCGF). Twenty-two patients (79%) responded to PWM + CM; 5 out of 5 patients responded to PWM + BCGF. The average mitotic index (+/- S.E.M.) for PWM, PMA, PWM + CM, PMA + CM, PWM + BCGF were 0.13 +/- 0.01, 0.24 +/- 0.13, 0.51 +/- 0.11, 0.14 +/- 0.06 and 0.63 +/- 0.15, respectively. Cytogenetic analysis revealed the presence of abnormal karyotypes in 22 patients. Fourteen patients (50%) had clonal chromosome aberrations which included: monosomy 1, 9, 17, 18, 21, and X chromosome, and trisomy of chromosomes 7, 9, 20, 21 and 22. The clonal structural aberrations were i(6q), inv(12) (q15q24), del(5) (p13p15), del(10) (q24). No homogeneously staining regions (HSR) were observed. Four patients with resistance to anti-neoplastic drugs showed the presence of double minute chromosomes (dmin) ranging in frequency from 5 to 50%.
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PMID:Clonal chromosomal changes in chronic lymphocytic leukemia. 230 14

Serum-free culture conditions would be preferable when studying the cellular and molecular regulation of B lymphocyte activation, proliferation and differentiation. We describe here the morphological and functional differentiation of chronic B-lymphocytic leukaemia (B-CLL) cells from 10 patients cultured in serum-free medium. When exposed to the phorbol ester TPA, cells from 8/10 cases expressed blastoid morphology and secreted significant levels of monoclonal IgM. The addition of 0.5% newborn calf serum to the serum-free medium increased both the spontaneous and TPA-induced IgM secretion of B-CLL cells by a factor of 6 and 7, respectively. Compared with TPA, significant but lower levels of IgM secretion and morphological differentiation were observed with native purified leucocyte interferon-alpha (IFN-alpha) (6/8 patients), some batches of recombinant IFN-alpha 2 (5/8 patients) and recombinant IFN-gamma (4/8 patients) in a dose-dependent and specific manner. Preactivation of B-CLL cells with TPA or anti-mu antibody was not necessary for the IFN-induced functional maturation. Significant DNA synthesis was not observed with any of the inducers used. These studies show that B-CLL cells can be induced to differentiate under serum-free conditions in response to physiological and non-physiological ligands.
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PMID:Induction of IgM secretion by chronic B-lymphocytic leukaemia cells in serum-free medium: effects of interferon-alpha, -gamma and phorbol ester. 245 Jul 4

T and NK cell blood subpopulations were determined in 33 patients with B-CLL and in 14 patients with B-MLUS by two-color immunofluorescence. CLL patients had significantly higher total numbers of Leu-7+ and CD8+ cells and lower numbers of CD16+/Leu-7- cells as well as a higher Leu-7/CD16 ratio and a lower CD4/CD8 ratio than MLUS patients and control donors. Moreover, MLUS patients exhibited a significantly lower Leu-7/CD16 ratio as well as a higher frequency of CD16+/Leu-7- cells than healthy donors. These results suggest that B-CLL patients have higher numbers of circulating immature NK cells compared to B-MLUS, while B-MLUS patients have a larger proportion of NK cells with a high lytic capability as compared to both CLL and normal controls. The imbalance between CD4+ and CD8+ cells was prominent in CLL with a low CD4/CD8 ratio, but within the upper normal range in MLUS. Differences in immunoregulatory cell subpopulations between B-CLL and B-MLUS might therefore contribute to the different clinical behavior of these two disorders.
Leukemia 1989 Jul
PMID:Differences in blood T and NK cell populations between chronic lymphocytic leukemia of B cell type (B-CLL) and monoclonal B-lymphocytosis of undetermined significance (B-MLUS). 247 2

A 78-year-old woman, who had axillary lymphadenopathy but no hepatosplenomegaly, was admitted because of lymphocytosis. The leukocyte count was 18.1 x 10(9)/l with 72% abnormal cells. Neither anemia nor thrombocytopenia was present. Many abnormal cells and erythroblasts were seen in the bone marrow. These abnormal cells had irregular nuclei but no granules in the cytoplasm. The surface markers of these cells were positive for E-rosette, CD 2, CD 3, and Leu 7 but negative for CD 4, CD 8, CD 11 (OKM 1), CD 16 (Leu 11), and HLA-DR. The DNA analysis revealed the rearrangement of T-cell receptor beta-chain genes. Direct Coombs test was positive and red-cell life-span (51Cr) was T 1/2 = 19.5 days. The patient was diagnosed as having T-CLL with mild autoimmune hemolysis and was followed without treatment. Seven months later, the leukemia cells of peripheral blood increased to 62.6 X 10(9)/l and the frank autoimmune hemolytic anemia developed. After prednisolone, vincristine and cyclophosphamide were administered, leukemia cells of blood decreased. Anemia with reticulocytopenia, however, persisted and direct Coombs test became negative. In the bone marrow at that time, many neutrophils and megakaryocytes besides leukemia cells were preserved, but erythroblasts were hardly seen, namely a pattern of red cell hypoplasia was observed. The patient deteriorated rapidly and died 26 months after initial recognition of lymphocytosis. When complement was added, the patient's serum obtained during red cell hypoplasia but not during autoimmune hemolysis inhibited BFU-E and CFU-GM in in vitro colony assays. This case indicates that not only B-CLL but also T-CLL is accompanied by immune hematocytopenia.
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PMID:[Red cell hypoplasia following autoimmune hemolytic anemia associated with T-CLL: report of a case and review of the literature]. 250 1

Normal B lymphocytes are characterized by rearrangement and expression of immunoglobulin genes, but not of T cell receptor genes. These properties might assist in lineage assignment, but there are examples of fresh leukemic cells and of cell lines where exceptions to this rule have been noted. We have studied cell samples of patients with B-CLL for expression of TCR alpha and beta chain genes. Using in situ hybridization with fluorescein-labeled probes, TCR alpha mRNA was found to be expressed in 14 of 18 samples and TCR beta mRNA in 7 of 16 samples. Specificity of hybridization was demonstrated by near complete blockade of TCR alpha hybridization with unlabeled TCR alpha, but not with unlabeled TCR beta probe. Furthermore, in Northern blot analysis a truncated 1,4 kb message for TCR alpha was readily detectable. No significant cell surface staining with the anti-TCR alpha/beta monoclonal antibody WT31 was observed. A contribution of T cells within the leukemic sample could be excluded since only samples with leukemic cell counts of greater than 50,000 cells/mm3 and only samples with 5% or less CD2+ T lymphocytes were studied. Our data show that a large proportion of B-CLL samples may express a truncated version of the TCR alpha message, indicating that this gene can be activated in leukemic B cells frozen at a late stage of differentiation.
Leukemia 1989 Jul
PMID:T cell receptor alpha expression in B-type chronic lymphocytic leukemia. 252 11


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