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)

We studied a variant CD5- B cell chronic lymphocytic leukemia (CLL) cell population that produces pathologic IgM kappa rheumatoid factor autoantibodies. In contrast to common CD5+ B cell CLL, this variant leukemia cell population displays intraclonal diversity in its expressed Ig V genes, similar to that noted for follicular B cell non-Hodgkin's lymphomas. Also, in contrast to common B cell CLL, these leukemia cells rapidly undergo cell death hours after being placed in tissue culture. We find that addition of Ag (aggregated human IgG) enhances significantly the survival of these cells in vitro. Leukemia cell survival also could be enhanced by exogenous IFN-gamma or anti-CD40 presented on Fc gamma RII (CDw32)-expressing L cells, but not by exogenous IL-4, IL-6, or monomeric human IgG. We find that Ag acts directly on the leukemia B cells to inhibit apoptosis. This effect could be mimicked by cross-linking the leukemia cells' surface IgM receptors with immobilized murine mAb specific for human Ig mu-chains, but not by immobilized mAb of irrelevant specificity. In contrast to most follicular NHL, this leukemia B cell population does not have evidence of bcl-2 gene rearrangement. Also, in contrast to non-Hodgkin's lymphomas and most B cell CLL, these cells do not express detectable amounts of bcl-2. Finally, although capable of inhibiting apoptosis, surface Ig receptor cross-linking does not induce expression of bcl-2 in these variant leukemia cells. We hypothesize that the lack of bcl-2 expression may render these leukemia cells particularly dependent upon the survival signal(s) derived from surface Ig receptor cross-linking. This state may represent an early stage in leukemia/lymphomagenesis, possibly accounting for the intraclonal diversity observed in the Ig V genes expressed by certain CD5- B cell leukemias and lymphomas.
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PMID:Autoantigen inhibits apoptosis of a human B cell leukemia that produces pathogenic rheumatoid factor. 750 24

The distribution and levels of three membrane proteins, CD35, CD46, and CD55, which serve as complement regulators, were examined in normal peripheral blood and hematologically malignant cells. CD35 was negative in most leukemia cells regardless of the type of leukemia, although granulocytes, monocytes, and some populations of lymphocytes were CD35+. CD46 was present in all blood cells except erythrocytes, and levels were 2-8 times higher in most leukemia cells than in their mature counterparts, particularly in CML and CLL cells, except for those of B cell lineage. CD55, a widely-distributed phosphatidyl inositol-anchored protein, was more frequently lost in NHL cells than in other types of hematological malignancies. In this review, we discuss the roles, mechanisms, and clinical applications of cell-associated complement regulatory proteins in hematological malignancies.
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PMID:Distribution of C3-step regulatory proteins of the complement system, CD35 (CR1), CD46 (MCP), and CD55 (DAF), in hematological malignancies. 751 63

PCR amplification of IgH gene V-D-J junctional variability (IgH PCR) is increasingly replacing Southern analysis for the detection of clonal lymphoid populations in cases presenting diagnostic difficulties. In order to determine the most efficient strategy, we have compared three known methods, using consensus primers against the VH FR3 or FR2 (FR256) regions, or a mix of six primers against the FR1 region (FR1f), with a new approach using a consensus primer against FR1 (FR1c), never previously described for diagnostic purposes, on DNA from 89 monoclonal B-cell proliferations (16 ALL, 28 CLL/PLL, 15 myelomas, 30 NHL). We obtained a detection rate of 70% for FR3, 64% for FR1f and 77% and 78% for FR256 and FR1c, respectively. Polyclonal lymphocytes and mature T cell malignancies tested negative for all systems. Differences in the detection rate were related not only to the choice of VH primer but also the JH primer(s) used and the pathological subtype. All strategies led to adequate detection of leukaemic DNA, whereas the detection rate in myeloma varied between strategies from 47 to 80% and that of follicular lymphoma from 13 to 63%. The lowest detection rates were observed in follicular lymphoma and in mature CD5 negative proliferations, reflecting the probable correlation between somatic mutation and PCR false-negativity. The combined use of FR1c and FR256 allowed detection in at least one system of 92% of cases overall and at least 75% in all pathological subtypes, thus providing a simple, reliable and rapid non-radioactive system for the detection of B cell clonality.
Leukemia 1995 Mar
PMID:Description of a novel FR1 IgH PCR strategy and its comparison with three other strategies for the detection of clonality in B cell malignancies. 753 68

We describe the occurrence of a variant Ph chromosome (v-Ph) in a therapy-related acute leukemia (s-AL), developed after 8-year treatment for a NHL with alkylating agents, anthracyclines and topoisomerase II inhibitors. The v-Ph originated from a complex t(2;9;22) translocation, expressed a p190bcr-abl fusion protein, and was associated to other specific changes, such as dup(3) (q21q26) and -7. The s-AL, apparently not preceded by a dysplastic phase, presented with signs of trilineage dysplasia with 10% micromegakaryocytes; it was classified as M5 according to FAB. The complex genetic changes observed in the present case may reflect distinct leukemogenic effects by different chemotherapeutic agents.
Leukemia 1995 Sep
PMID:Acute leukemia presenting a variant Ph chromosome with p190 expression, dup 3q and -7, developed after malignant lymphoma treated with alkylating agents and topoisomerase II inhibitors. 765 16

From 1986 through 1990, 13 previously untreated pediatric patients with advanced diffuse large-cell non-Hodgkin's lymphoma (LC-NHL) were treated with a 12-week MACOP-B regimen at St Jude Children's Research Hospital. Although 12 patients (92%) achieved a complete response, and one had a partial response, the 2-year event-free survival was only 54 +/- 15% (SE). Seven patients remain in continuous complete remission at a median of 40 months after therapy (range 23-57 months). Relapses occurred at sites of initial involvement in five patients at a median of 3.0 months after remission (range 1.2-8.5 months). Salvage therapy with radiation, and high-dose chemotherapy and bone marrow transplantation produced four durable second remissions. The 2-year overall survival for the entire group is 84 +/- 10% (SE). The 12-week MACOP-B regimen proved feasible in an ambulatory clinic setting with only minimal toxicity. We found that MACOP-B is an effective and tolerable treatment for pediatric patients with LC-NHL but did not provide improved survival over that of a similar group of children treated in previous trials at this institution.
Leukemia 1993 Feb
PMID:MACOP-B treatment in children and adolescents with advanced diffuse large-cell non-Hodgkin's lymphoma. 767 78

From April 1988 to May 1993, 71 patients (32 acute myelogenous leukaemia [AML], 24 acute lymphoblastic leukaemia [ALL], 7 Hodgkin's disease [HD], 5 non-Hodgkin lymphoma [NHL], 2 neuroblastoma, 1 chronic myelogenous leukaemia [CML]) were treated with myeloablative therapy followed by reinfusion of cryopreserved autologous bone marrow (ABMT). The majority of patients with acute leukaemia were in first complete remission (CR), while 11 AML patients and 9 ALL patients were in advanced stage of the disease (> I CR or relapse). The BM was reinfused without purging. The conditioning regimen for all ALL and proportion of AML patients consisted of cyclophosphamide (CY) 120 mg/kg and fractionated total body irradiation (TB) in a total dose of 12 Gy. 18 AML patients received busulfan 16 mg/kg instead of TBI. Leukaemia-free survival (LFS) for first CR AML patients was 48% at 43 months with the median follow-up of 17 months. Probability of relapse was 44%. LFS for advanced AML was only 9% and the probability of relapse 89%. LFS for first CR ALL patients was 72% at 53 months with the median follow-up of 15 months, while probability of relapse was only 23%. For advanced ALL, LFS was 32% at 33 months and probability of relapse 64%. Probability of toxic death for first CR patients was 11%. We found a predictive value of viability testing and in vitro CFU-GM assay for haematologic recovery after ABMT. We conclude that ABMT with cryopreserved BM is a relatively safe method for consolidation therapy of AL. The results of treatment are encouraging.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autologous bone marrow transplantation for haematological malignancies--experiences of the centre of Zagreb. 776 56

The FMS proto-oncogene encodes a polypeptide growth factor receptor expressed on the cell surface of monocytes and B lymphocytes within the haematological system. Mutations of the FMS gene at codons 301 and 969 have been detected in a number of haematological disorders. Mutations at these codons are thought to be important in the pathogenesis of leukaemia in cells expressing a mutant receptor. Following our finding that the colony stimulating factor-1 receptor (CSF-1R) was expressed on B cells, we have assessed DNA from 17 patients with B-cell chronic lymphocytic leukaemia (CLL), 15 with acute lymphoblastic leukaemias (ALL), two samples from patients with B-cell non-Hodgkin's lymphoma (B-NHL), and 20 haematologically normal individuals for the presence of C-terminal mutations of the FMS gene. Using single stranded conformational polymorphism analysis (SSCP), a single band shift was detected resulting from a nucleotide insertion at codon 965 in the DNA isolated from a patient with B-NHL. These results indicate that mutations of the FMS gene in this region are rare in B-cell malignancy but may contribute to the pathogenesis of leukaemias and lymphomas in a small subset of patients. However, the presence of other mutations not detected using this type of analysis cannot be excluded.
Leukemia 1995 Jan
PMID:A C-terminal FMS mutation in a patient with B-cell malignancy. 784 11

12 cases of ALL, 2 cases of ANLL and 3 cases of NHL have been registered among children aged 0-15 living in 6 Bryansk territory regions exposed to radionuclide contamination after the Chernobyl accident. The study covers the period from 1986 to 1991. There was an excess of acute Leukemia incidence in 1986 as indicated by 7 ALL and 1 ANLL cases. For ALL relative risk was 4.49, p = 0.006. In 2 cases AL was diagnosed before the accident, 2 patients fell ill in June, 2 in July, 1 in August, we have no exact date for 1 patient. Relative risk has never exceeded 1.0 for all the analyzed hemoblastoses within the last 5 years. The Poisson probability of chance occurrence of 8 AL cases in supervision regions during one year is 0.0004. Sex distribution of the cases was atypical either: 7 from 8 patients were boys. Binomial probability is 0.056 under the standard sex ratio 6:5. No evidence was obtained that this high incidence of childhood leukemia extends to neighbour regions of the Gomel, Mogilev and Bryansk territories. The descriptive epidemiological analysis has confirmed the existence of childhood leukemia incidence excess in 1986, but failed to explain its cause. Analysis of incidence rates alone is not enough to confirm connection between leukemia hazard and Chernobyl accident.
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PMID:[Descriptive analysis of the excess of acute leukemia morbidity among children in Briansh district]. 789 37

The WT1 gene encoding a zinc finger polypeptide is a tumor suppressor gene that plays a key role in the carcinogenesis of Wilms' tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine relative levels of WT1 gene expression (defined in K562 cells as 1.00) in 45 patients with acute myelogenous leukemia (AML), 22 with acute lymphocytic leukemia (ALL), 6 with acute mixed lineage leukemia (AMLL), 23 with chronic myelogenous leukemia (CML), and 24 with non-Hodgkin's lymphoma. Significant levels of WT1 gene were expressed in all leukemia patients and for CML the levels increased as the clinical phase progressed. In striking contrast with acute leukemia, the levels of WT1 gene expression for NHL were significantly lower or even undetectable. Clear correlation was observed between the relative levels of WT1 gene expression (< 0.6 v > or = 0.6) and the prognosis for acute leukemia (AML, ALL, and AMLL). Patients with less than 0.6 levels had significantly higher rates of complete remission (CR), disease-free survival, and overall survival than those with > or = 0.6 levels, whereas CR could not be induced in any of the 7 patients with acute leukemia having greater than 1.0 levels of WT1 gene expression. The quantitation of the WT1 gene expression made it possible to detect minimal residual disease (MRD) in acute leukemia regardless of the presence or absence of tumor-specific DNA markers. Continuous monitoring of the WT1 mRNA was performed for 9 patients with acute leukemia. In 4 patients, MRD was detected 2 to 8 months before clinical relapse became apparent. In 2 other patients, the WT1 mRNA gradually increased after discontinuation of chemotherapy. No MRD was detected in the remaining 3 patients with AML who received intensive induction and consolidation therapy. Simultaneous monitoring of MRD by RT-PCR using primers for specific DNA markers in 3 patients (2 AML-M3 with PML/RAR alpha, and 1 AML-M2 with AML1/ETO) among these 9 patients detected MRD comparable with that obtained from quantitation of WT1 gene expression. In a patient with acute promyelocytic leukemia, the limits of leukemic cell detection by RT-PCR using either WT1 or promyelocytic leukemia/retinoic acid receptor-alpha gene primers were 10(-3) to 10(-4) and 10(-4) for bone marrow, and 10(-5) and 10(-4) for peripheral blood, respectively. Therefore, we conclude that WT1 is a new prognostic factor and a new marker for the detection of MRD in acute leukemia.
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PMID:WT1 as a new prognostic factor and a new marker for the detection of minimal residual disease in acute leukemia. 794 79

A phenotypic and molecular evaluation was made of 15 patients with mature B-cell leukemia/lymphoma showing exclusive spleen and bone marrow involvement. According to French-American-British criteria, these cases could not be classified as classical B-cell chronic lymphocytic leukemia, hairy cell leukemia and its variant forms, splenic lymphoma with villous lymphocytes, or leukemic phase non-Hodgkin's lymphoma (NHL; follicular or intermediate type). The immunophenotype pattern (high surface Ig and CD25 expression, and little or no reactivity with CD5, CD23, and CD11c) and cytomorphologic features of these neoplasms suggested an origin in the marginal zone of the spleen. Molecular analysis did not show any involvement of the dominantly acting oncogenes generally associated with lymphoid malignancies (c-myc, bcl-2, bcl-1, Ras), but mutations of the p53 tumor suppressor gene involving exons 5, 6, and 8 were found in 6 cases (6 of 15, 40%). In 4 cases, the p53 alterations consisted of a point mutation leading to amino acid substitution. In the remaining 2 cases, an insertion or deletion resulting in a frame-shift of the protein was observed. In all but 1 of the cases, the wild-type sequence at the mutation site was barely visible, implying the loss of the normal p53 allele in leukemic cells. All of the cases showed a clinical course compatible with that of low-grade NHL, regardless of the p53 loss/mutation. Overall, our data suggest the existence of a form of splenic B-cell leukemia/lymphoma of possible marginal zone origin in which p53 inactivation may play an important pathogenetic role.
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PMID:Frequent p53 gene involvement in splenic B-cell leukemia/lymphomas of possible marginal zone origin. 801 22


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