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

Now that a substantial group of cancer patients has such a favourable prognosis, it has become increasingly important to evaluate the long-term complications of treatment. Of all late effects of treatment, secondary leukaemia is one of the most serious. Increased risk of AML has been observed both after RT and after CT; however, several types of CT have much stronger leukaemogenic properties than RT. Limited field radiation in the therapeutic dose range is associated with very little or no increased risk of leukaemia, which has been attributed to cell killing at the higher radiation doses. With respect to CT, two different syndromes of treatment-related AML have been recognized. Risk of alkylating agent-related AML is highest in the 5-10 year follow-up period and seems to decrease afterwards. This type of leukaemia is often preceded by MDS, and is characterized by deletions of chromosomes 5 and 7. Leukaemias related to treatment with the topoisomerase II inhibitors are characterized by a short induction period, presentation as myelomonocytic or monocytic leukaemia (rather than MDS) and balanced chromosomal translocations involving bands 11q23 and 21q22. This review addresses the risk of secondary AML and MDS following treatment of HD, NHL, testicular cancer, ovarian cancer, breast cancer and paediatric malignancies. In patients with HD, the risk of AML is higher with an increasing number of mechlorethamine-procarbazine-containing cycles, a greater number of CT episodes, and after splenectomy. The majority of data shows that RT does not add to the leukaemia risk from CT, but this issue is still surrounded by some controversy. ABV(D)-treated patients have a very low risk of AML. Generally, patients with NHL, testicular cancer and breast cancer experience much lower risk of AML than patients with HD. NHL and breast cancer treatment regimens with cumulative cyclophosphamide doses of 20 g or less do not confer an appreciable increase of AML. Recently, strongly increased AML risk has been observed following autologous bone marrow transplantation and other dose intensification strategies. Risk factors for this excess remain to be defined. PVB treatment for testicular cancer is not followed by increased leukaemia risk, but modern etoposide-containing regimens do confer excess risk, of which the magnitude at conventional drug doses is not yet well known. High risk of leukaemia has been reported in children treated with epipodophyllotoxins. The leukaemogenic hazards of cancer treatment should be weighed against their therapeutic benefits.
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PMID:Risk of acute myelogenous leukaemia and myelodysplasia following cancer treatment. 873 May 51

We conducted an ultrastructural study in 22 cases of B-lymphoproliferative disorders in leukaemic phase bearing the t(11;14) translocation. The features of peripheral blood leukaemic cells in nine cases of mantle cell lymphoma (MCL) were compared to those diagnosed as B-prolymphocytic leukaemia (B-PLL) (five cases), splenic lymphoma with villous lymphocytes (SLVL) (four cases), lymphoplasmocytic lymphoma (LPL) (one case), chronic lymphocytic leukaemia with > 10% prolymphocytes (CLL/ PL) (one case) and unclassified B-non Hodgkin's lymphoma (B-NHL) (two cases). The ultrastructural characteristics were also compared to those present in B-NHL without t(11;14), including cases of follicular centre lymphoma (FCL). This study shows that MCL has distinct ultrastructural features including a cleaved or indented nucleus with an even heterochromatin distribution, an absent or inconspicuous nucleolus, low N/C ratio, abundant mitochondria, a well developed Golgi zone, profiles of endoplasmic reticulum and centrioles. This pattern clearly differs from that found in FCL cells. The nuclear pattern of MCL cells also differed from the cells in the other disorders with t(11;14), but shared an organelle-rich cytoplasm, and features which were not apparent in cases without t(11;14). The cytoplasmic changes observed in cells bearing t(11;14) suggest increased cellular activity which may relate to the chromosome translocation and the resulting over-expression of bcl-1.
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PMID:The ultrastructure of mantle cell lymphoma and other B-cell disorders with translocation t(11;14)(q13;q32). 875 96

It has been recognized that clonal T-cell receptor delta (TCR delta) gene rearrangement is present in both T-and B-cell malignancies. The highly sensitive polymerase chain reaction (PCR) technique may be applicable to cases of leukemia and lymphoma of non-T-cell origin for detection of minimal residual disease (MRD). A PCR technique was used in this study to investigate the pattern of clonal TCR delta gene rearrangement in Hong Kong Chinese patients with non-T-cell hematological malignancies. Seventy-three patients with the diagnosis of acute leukemia and non-Hodgkin's lymphoma of non-T-cell origin were included in this study. There were 20 patients with common ALL (cALL), seven precursal B-cell ALL (PreB-ALL), 23 acute myeloid leukemia (AML), and 23 non-Hodgkin's lymphoma of B-lineage (B-NHL). Clonal rearrangement was detectable by Southern analysis using a J delta 1 probe in 41 per cent of ALL of B-lineage but in none of the B-NHL or AML. The samples were also studied further by monoclonal PCR amplification for TCR delta gene rearrangement. Three different sets of primers were employed to detect clonal rearrangement of the TCR delta gene. The V delta 1(D)J delta 1 recombination typically seen in T-cell malignancies were not seen in any of the of the non-T-cell malignancies. The V delta 2 (D) D delta 3 recombination was found exclusively in ALL of B-lineage and was seen in 73 per cent of the Southern positive cases. Although clonal TCR delta gene rearrangement was undetectable by Southern analysis in our AML cases, 26 per cent had a V delta 2(D)J delta 1 recombination found by the PCR technique. Sensitivity of the PCR technique was determined by serial mixing and was up to 5-10 leukemic cells per 10(4) nucleated cells. It was apparent from this study that it was feasible to detect clonal TCR delta gene rearrangement by the PCR technique in a proportion of the cases of non-T-cell hematological malignancies. The PCR technique can be applied to detect residual leukemic cells in marrow of patients in an apparent morphological complete remission. The value of this application requires further clinical evaluation and correlation.
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PMID:Pattern of T-cell receptor delta gene rearrangement by Southern blotting and polymerase chain reaction technique in Hong Kong Chinese patients with non-T-cell hematological malignancies. 887 35

The human PRDI-BF1 or BLIMP1 gene and its mouse homolog Blimp1 are members of the recently realized PR domain family that includes the retinoblastoma interacting zinc finger gene RIZ and the MDS1-EVI1 leukemia cancer gene. The specific high-level expression of Blimp1 in late B and plasma cells, its induction during B-cell differentiation, and its ability to drive B-cell maturation suggest that this gene may play a role in the differentiation and pathogenesis of B cells. We have now mapped the physical location of BLIMP1 near the marker D6S447 on human chromosome 6q21-q22.1; we have also mapped Blimp1 to mouse Chromosome 10 at 14 cM distal to the Myb locus and to a region homologous to the location of BLIMP1. Deletions of the 6q21-q22 region are common in several human malignancies, particularly in B-cell non-Hodgkin lymphoma (B-NHL). The data led us to suggest that BLIMP1 may be a candidate B-NHL tumor suppressor gene.
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PMID:The B-lymphocyte maturation promoting transcription factor BLIMP1/PRDI-BF1 maps to D6S447 on human chromosome 6q21-q22.1 and the syntenic region of mouse chromosome 10. 892 66

Abnormalities of several cell-cycle regulatory genes including cyclin D1, p16CDKN2 and p15CDKN2B have been described in B cell non-Hodgkin's lymphoma (B-NHL). We describe a new B-NHL cell line (Granta 519), with concurrent abnormalities of the cyclin D1, pl6CDKN2 and pl5CDKN2B genes. An independent clinical case of mantle cell NHL (Mc-NHL) with concomitant overexpression of cyclin D1, and deletion of the p16CDKN2 gene was also identified, suggesting that this combination of oncogenic aberration is a pathophysiologic contribution to a subset of NHL cases. More in-depth functional studies of this concept were facilitated by the availability of the cell line Granta 519 which was derived from a case of high-grade NHL and has a mature B cell immunophenotype. Cytogenetic analysis identified translocation t(11;14)(q13;q32) and complex rearrangements involving chromosomes 9p22, 13p21, 17pl1, and 18q21. Molecular analysis identified overexpression of cyclin D1 mRNA and biallelic deletion of the p16CDKN2 and p15CDKN2B genes. To elucidate the effect of these genetic abnormalities on the G1 control of Granta 519 cells, the level and function of the major components of the cyclinD/retinoblastoma (RB) pathway were investigated. Cyclin D1 was dominant among the D-type cyclins, formed abundant complexes with cyclin-dependent kinase (Cdk) Cdk4 rather than Cdk6, and the immunoprecipitated cyclin D1/Cdk4 holoenzyme was active as a pRB kinase. Electroporation of wild-type pl6CDKN2 arrested the Granta 519 cells in G1, consistent with the p16CDKN2 loss as a biologically relevant event during multistep evolution of the tumor, and with the expression of functional pRB. Direct cooperation of these distinct abnormalities to cell-cycle, deregulation in NHL cells was suggested by G1 acceleration upon inducible overexpression of cyclin D1 in a control breast cancer cell line lacking p16CDKN2, an effect which could be prevented by ectopic expression of p16CDKN2. Taken together, these data suggest that concurrent overexpression of cyclin D1 and functional elimination of p16CDKN2 and p15CDKN2B may characterize certain cases of mantle cell NHL, and that cooperation of the abnormalities is likely to provide a growth advantage of the tumour cells through more efficient inactivation of the RB tumor suppressor. Further clinicopathologic studies of this possibility are warranted.
Leukemia 1997 Jan
PMID:Potential role for concurrent abnormalities of the cyclin D1, p16CDKN2 and p15CDKN2B genes in certain B cell non-Hodgkin's lymphomas. Functional studies in a cell line (Granta 519). 900 20

Hairy-cell leukaemia may be difficult to diagnose in bone marrow biopsies, especially in the early stages or in its residum after complete clinical remission. To consider the impact of published data on immunophenotyping hairy-cell leukaemias, a total of 50 diagnostic biopsies were systematically analysed with a panel of eight antibodies and compared with cases of chronic lymphatic leukaemia (CLL), 20 follicular centre lymphomas, 20 lympho-plasmacytoid immunocytomas, 10 small-cell T-cell non-Hodgkin lymphomas and 20 cases of benign nodular lymphatic hyperplasia. The panel of eight antibodies comprised DBA44, CD45, CD20, CD45R, CD45RO, CD43 and the CD68 antibodies KP1 and Ki-M1P. The hairy-cell leukaemias were staged histologically into four categories of bone marrow infiltration. DBA44 reacted positively in 47/50 cases. CD45 and the B-cell markers CD20 and CD45R reacted in 49/50 and 43/50 cases, respectively. One CD68 marker, KP1, was positive in 38/50 cases but the other-Ki-M1P-only in 1/50 cases. Chronic lymphatic leukaemia cases, the other B-cell NHLs and lymphatic hyperplasias showed strong positivity for CD20 and CD45R, but only the immunocytomas reacted with DBA44 in 7/20 cases. The T-cell NHLs and hyperplasias showed a strong positivity for the T-cell markers CD45RO and CD43. The CD68-marker Ki-M1P revealed a high specificity since it was negative in all NHLs and positive only in one hairy-cell leukaemia. Methyl-methacrylate embedding of bone marrow biopsies under cold polymerization produces a high quality of histo- and cytomorphology, resulting in greater diagnostic reliability and the detection of low-stage infiltration of hairy-cell leukaemia. DBA44 appears as a highly specific antibody to mark hairy-cells since only immunocytomas reacted positively in a few cases. A small panel of antibodies including DBA44. CD20, CD45R and Ki-M1P may serve to distinguish small-cell. NHL from hairy-cell leukaemia even at an early stage or when there are minimal residual tumour cells.
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PMID:Immunophenotype of hairy-cell leukaemia after cold polymerization of methyl-methacrylate embeddings from 50 diagnostic bone marrow biopsies. 906 39

We evaluated 1179 consecutive patients with low-grade B-NHL diagnosed according to criteria of the Kiel classification and presenting with initial bone marrow involvement. Therapeutic approaches were not changed during the observation period 1975-1995. CLL (n=895) and IC (n=169) were treated palliatively with chlorambucil/prednisone or prednimustine. In CBCC (n=65) and CC (n=50) remission was induced with COP or CHOP. The overall response rate was 67%, but only 35% of CBCC and 23% of CC patients achieved complete remission. Median survival was 64 months in CBCC and 28 months in CC. As the median age of our patient population was 68 years (range: 23-93) it seems doubtful whether overall prognosis can be improved by aggressive therapeutic measures. One exception might be CBCC patients who were younger (median age 56 years) and who were usually in good general condition so that they might qualify for high dosage chemotherapy and stem cell support. Whether the prognosis of IC and CLL (median survival 74 months and 107 months, respectively) can be improved by treatment with drugs such as purine analogs will depend on the long-term outcome of clinical studies.
Leukemia 1997 Apr
PMID:Outcome of patients with low-grade B cell non-Hodgkin lymphoma and initial bone marrow involvement: data of a single institution. 917 41

Fludarabine is an antineoplastic agent which has been studied in patients with a variety of lymphoproliferative malignancies. Clinical evidence from comparative studies in chronic lymphocytic leukaemia (CLL) suggests that fludarabine is at least as effective as CAP (cyclophosphamide, doxorubicin and prednisone) or CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) in previously treated or chemotherapy-naive patients and significantly more effective than chlorambucil in terms of response rate and duration and survival in chemotherapy-naive patients. Promising results have also been reported with fludarabine-based combination therapy in the treatment of patients with CLL. In addition, sequential therapy with fludarabine and cytarabine has demonstrated good efficacy in the treatment of acute leukaemias, as has fludarabine monotherapy and combination therapy in low grade non-Hodgkin's lymphoma. A favourable cytoreductive response has been reported in patients with lymphoplasmacytoid lymphoma and in a smaller number of patients with cutaneous T cell lymphomas, CLL of T cell origin or prolymphocytic leukaemia. Recent data also support the use of fludarabine, either as a component of a nonmyeloablative conditioning regimen or in the attainment of minimal residual disease, in patients undergoing peripheral blood stem cell or bone marrow transplantation. The tolerability profile of fludarabine is similar to that of CAP, with the most common adverse events being granulocytopenia, thrombocytopenia, anaemia and infection. Alopecia and nausea/vomiting appear to be less frequent with fludarabine therapy than with CAP although the development of immune cytopenias is more frequent with fludarabine. Severe neurotoxicity has been reported with fludarabine but this is mostly confined to the use of high doses. Clinical experience therefore indicates that fludarabine is an effective and generally well-tolerated antineoplastic agent for the second-line treatment of advanced CLL. Recent data from comparative studies also support the earlier use of fludarabine in the treatment of chemotherapy-naive patients with CLL. Furthermore, results of available studies are increasingly highlighting an important future role for fludarabine in the treatment of acute leukaemias and low grade NHL and possibly other lymphoproliferative disorders, particularly when used as a component of combination chemotherapy.
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PMID:Fludarabine. An update of its pharmacology and use in the treatment of haematological malignancies. 917 29

We describe a patient presenting with systemic lupus erythematosus (SLE) and concomitant low-grade (Ig) non-Hodgkin's lymphoma of the B cell type (B-NHL). Although the association of autoimmune disorder and lymphoma is well conceived, there is only scarce information available as to the simultaneous occurrence of both disease conditions in one patient. As in this patient diagnosis of Ig B-NHL was also based on the detection of a monoclonal population of CD5+ B lymphocytes, and given that the polyclonal expansion of CD5+ B cells has been previously reported in rheumatoid arthritis (RA), Sjogren's syndrome (SS) and single cases of SLE, the observations we made in this patient led us to discuss the role of the CD5+ population in the development of rheumatic disorders and concomitant lymphoid malignancy. Moreover, since impaired production rates of interleukin 3 (IL-3) and interleukin 4 (IL-4) have been associated with an abnormal expansion of CD5, lymphoma cells and seeing that soluble interleukin 2 receptor (sIL-2R) serum levels were found to be positively correlated with disease activity both in SLE and Ig B-NHL, these parameters were investigated and related to the patient's disease state throughout the entire clinical observation period.
Leukemia 1997 Aug
PMID:Concomitant manifestation of systemic lupus erythematosus and low-grade non-Hodgkin's lymphoma. 926 88

Ataxia-telangiectasia (A-T) is a recessive multi-system disorder caused by mutations in the ATM gene at 11q22-q23 (ref. 3). The risk of cancer, especially lymphoid neoplasias, is substantially elevated in A-T patients and has long been associated with chromosomal instability. By analysing tumour DNA from patients with sporadic T-cell prolymphocytic leukaemia (T-PLL), a rare clonal malignancy with similarities to a mature T-cell leukaemia seen in A-T, we demonstrate a high frequency of ATM mutations in T-PLL. In marked contrast to the ATM mutation pattern in A-T, the most frequent nucleotide changes in this leukaemia were missense mutations. These clustered in the region corresponding to the kinase domain, which is highly conserved in ATM-related proteins in mouse, yeast and Drosophila. The resulting amino-acid substitutions are predicted to interfere with ATP binding or substrate recognition. Two of seventeen mutated T-PLL samples had a previously reported A-T allele. In contrast, no mutations were detected in the p53 gene, suggesting that this tumour suppressor is not frequently altered in this leukaemia. Occasional missense mutations in ATM were also found in tumour DNA from patients with B-cell non-Hodgkin's lymphomas (B-NHL) and a B-NHL cell line. The evidence of a significant proportion of loss-of-function mutations and a complete absence of the normal copy of ATM in the majority of mutated tumours establishes somatic inactivation of this gene in the pathogenesis of sporadic T-PLL and suggests that ATM acts as a tumour suppressor. As constitutional DNA was not available, a putative hereditary predisposition to T-PLL will require further investigation.
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PMID:Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia. 928 6


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