Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The breakpoint localization was analyzed in 61 patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia to compare the breakpoint localization and clinical course. All patients were treated with interferon alfa (IFN alpha) or IFN alpha plus IFN gamma at the time of the study. Thirty-three of the patients had been pretreated with other cytostatic drugs. Sixty-nine per cent of the breakpoints were located in the 5' region of the major breakpoint cluster region (M-bcr), 29% in the 3' part. There was no significant difference between these two groups with respect to response to IFN(s), clinical course or conversion to blast crisis, nor survival.
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PMID:Breakpoint localization within the M-bcr and clinical course do not correlate in patients with chronic myelogenous leukemia undergoing alfa interferon therapy. 205 69

A 64-year-old woman presented with a platelet count of 3,225 x 10(9)/L. Bone marrow morphology showed massive megakaryocytic hyperplasia; cytogenetic studies showed the presence of the Philadelphia chromosome (Ph). The presence of a rearrangement involving the major breakpoint cluster region (mbcr) on chromosome 22 was confirmed by Southern blotting techniques. A diagnosis of Ph positive essential thrombocythemia (ET) was made. Such cases constitute less than 5% of patients with ET and it has been proposed that they be considered examples of chronic myelogenous leukemia (CML) because of a shared propensity to progress to blast crisis. An argument is presented for retaining Ph positive ET as an entity separate from Ph negative ET and Ph positive CML.
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PMID:Essential thrombocythemia with the Philadelphia chromosome and BCR-ABL gene rearrangement. An entity distinct from chronic myeloid leukemia and Philadelphia chromosome-negative essential thrombocythemia. 206 12

We studied breakpoints within the first intron of the BCR gene in 28 Philadelphia (Ph1)-positive acute leukemias (AL) and one Ph1-positive chronic myelogenous leukemia (CML), which lacked rearrangement of major breakpoint cluster region. With a series of genomic probes from this intronic region, we have detected chromosomal breaks in 19 of 28 patients with Ph1-positive AL and one patient with CML. Breakpoints were all located within 30 kb region at the 3' portion of the intron, same as in the previously reported cases. Breakpoints in our cases were not limited within "bcr-2" or "bcr-3", proposed by Chen, et al., but, occurred within or near Alu sequences. Our findings suggest that breakpoints are not randomly distributed throughout this intron, but, there may be some specific sequences that facilitate the process of chromosomal translocation.
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PMID:[Detection and localization of breakpoints within the first intron of the BCR gene in Ph1-positive leukemias]. 206 74

Acute lymphoblastic leukemia (ALL) patients with a Philadelphia chromosome (Ph+ ALL) were treated with a combination of antineoplastic drugs recommended for both myeloid and lymphoid leukemia (BHAC-DMPV: behenoylcytosine arabinoside, daunorubicin, 6-mercaptopurine, prednisolone, and vincristine). Ph+ ALL patients with chromosome breaks which occur within the major breakpoint cluster region (M-BCR rearranged Ph+ ALL) were treated with natural interferon-alpha (IFN-alpha) after entering complete remission. In this study, four of seven patients with Ph+ ALL had M-BCR rearrangement, and all achieved complete remission with karyotypic normalization. Subsequent cytogenetic analysis during complete remission in two ALL patients with M-BCR rearrangement revealed that the percentage of bone marrow cells with the Ph chromosome increased, while the bone marrow maintained remission status. This cytogenetic-hematological discrepancy led us to consider that M-BCR rearranged Ph+ ALL might be a variant of chronic myelogenous leukemia, therefore, three Ph+ ALL patients with M-BCR rearrangement were treated with IFN-alpha after achieving complete remission. In contrast, only one of three patients with M-BCR non-rearranged Ph+ ALL obtained complete remission.
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PMID:Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia: a pilot study which raises important questions. 207 47

Essential thrombocythemia (ET) is a myeloproliferative disorder characterized by a platelet count higher than 1000 x 10(9)/l. Bone marrow karyotype aberrations are occasionally observed. The presence of cytogenetic and molecular markers of chronic myeloid leukemia (CML) was assessed in 25 patients with the clinical features of ET. One displayed a complex translocation (9; 15; 22) (q34.1 or q34.3; q26.1; q11), and another a Philadelphia chromosome with standard translocation (9; 22) (q34; q11). Southern blot analysis revealed a rearranged breakpoint cluster region (bcr) in each case. Both patients experienced a stormy disease course without a leukemic transformation. These data indicate that the Philadelphia chromosome rarely occurs in ET and strongly influences patient outcome.
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PMID:Analysis of the breakpoint cluster region in essential thrombocythemia. 209 1

Two patients with plasma cell dyscrasia and IgG lambda paraproteinemia in association with the rare disorder, chronic neutrophilic leukemia (CNL), are described. Cytogenetic studies excluded Philadelphia + chronic myeloid leukemia and molecular analysis of the breakpoint cluster region (bcr) revealed no evidence of clonal gene rearrangement. Nine similar cases of coexistent CNL and paraproteinemia have been identified in the literature and attention is drawn to the disproportionate excess of lambda light chain restriction in this subset of patients. Evidence supporting a clonal origin of CNL is considered and the nature of the relationship between the chronic myeloid expansion and the development of multiple myeloma is discussed.
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PMID:Chronic neutrophilic leukemia and multiple myeloma. An association with lambda light chain expression. 211 78

A 42-year-old woman presented with clinical and haematological features of essential thrombocythaemia (ET). Cytogenetic investigation revealed a standard t(9;22) Philadelphia translocation in all evaluable metaphases which persisted throughout treatment. Gene probe analysis of the chromosome 22 breakpoint cluster region (bcr) locus revealed a breakpoint mapping between exons 1 and 3 of the bcr gene, consistent with a standard bcr-abl translocation as found in chronic myeloid leukaemia (CML). Moreover, in separate cell populations, the bcr breakpoint was demonstrable in DNA from granulocytes but not in T cells from either peripheral blood or bone marrow. Since ET is known to be a clonal disorder with a multipotential stem cell origin, these findings suggest that, as in CML, the bcr-abl hybrid gene arises through translocation in a multilineage stem cell which does not involve the T lymphocyte lineage.
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PMID:The t(9;22) translocation in Philadelphia-positive essential thrombocythaemia does not involve the T lymphocyte lineage. 214 47

We have analyzed the configuration of the immunoglobulin heavy (IgH) chain gene and the T cell receptor (TCR) chain (beta, gamma, and delta) genes in a group of 22 leukemia patients with the Philadelphia (Ph) chromosome. The group consisted of 14 patients with chronic myelogenous leukemia in blast crisis (CML-BC) and eight with Ph-positive acute leukemia (Ph + AL); these diagnoses were based on hematologic and cytogenetic features. In CML-BC patients, an IgH joining region rearrangement was detected only in patients with CD10 expression; TCR-beta, -gamma, or -delta rearrangements were associated with IgH involvement. In contrast, five of the eight Ph+ AL patients had breaks within the major breakpoint cluster region (M-BCR), and four of them had IgH involvement. Of the remaining three Ph+ M-BCR nonrearranged AL patients, only one showed IgH rearrangement. In addition, TCR-beta involvement was sometimes detected in Ph+ AL patients (two of the eight patients) with or without rearranged M-BCR, and no PH+ AL case displayed rearranged TCR-gamma. These findings suggest that genotypic changes in CML-BC are usually associated with phenotypic results of the neoplastic cells: the expression of CD10 in CML-BC patients is accompanied by the involvement of IgH with frequent TCR rearrangements which possibly are due to the common recombinase activity. On the other hand, the mechanism of the involvement of IgH in Ph+ AL patients without rearranged M-BCR seems different from that observed in Ph+ leukemia patients with rearranged M-BCR, although TCR involvement could occur whether or not the leukemia cells had a rearranged M-BCR in Ph+ AL patients.
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PMID:Immunoglobulin and T cell receptor gene rearrangements in Philadelphia chromosome-positive leukemia: a different involvement pattern in blast crisis and acute leukemia. 214 95

We demonstrated the clinical effectiveness of recombinant interferon-gamma (rIFN gamma) (Biogen) in 18 patients with Philadelphia-positive chronic myeloid leukemia. Sequential cytogenetic studies and molecular analyses of the breakpoint cluster region and for immunoglobulin and T cell rearrangements were performed every 3-4 months. In 13 patients who received treatment for a minimum of 3 months, the majority were treated with 1.5 mg/m2, t.i.w., i.v. Nonhematologic effects--particularly chills, rigors, myalgia, fatigue, headaches, and nausea--were significant. Complete or partial hematologic responses were observed in six patients, two of whom had approximately 20% normal metaphases after an average of 74 weeks of treatment. However, reversion to 100% Ph+ cells occurred 30 weeks later. In these two patients, in whom normal metaphases were found, no changes were observed in the presence of rearrangements of the breakpoint cluster region. In addition, the marrows remained hypercellular, and the leukocyte alkaline phosphatase score and B12 levels remained abnormal. No immunoglobulin or T cell beta-chain gene rearrangements were found. These data indicate the clinical effectiveness of rIFN gamma in some patients with chronic myeloid leukemia, although the fundamental nature of the disease is unaltered by this form of treatment.
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PMID:Recombinant gamma-interferon has activity in chronic myeloid leukemia. 215 24

We report two cases of Philadelphia (Ph1) chromosome positive acute mixed lineage leukemia (AMLL) with breakpoint cluster region (bcr) (M-BCR-1) rearrangement. A 31 year-old-man (case 1) and a 42 year-old-woman (case 2) were admitted to our hospital for further evaluation of leucocytosis with atypical blasts. Each case was diagnosed as having bilineal type of AMLL because: (1) blasts in each case consisted of larger myeloid cells positive for myeloperoxidase and small lymphoid cells positive for PAS, and blasts in case 2 were positive for TdT; (2) blasts in case 1 expressed B lymphoid associated antigen; (3) Southern analysis in each case showed clonal rearrangements of both the immunoglobulin heavy chain and the T cell receptor beta gene. These two cases demonstrated the Ph1 chromosome and rearrangement of the bcr (M-BCR-1) gene, but none of splenomegaly, basophilia, and additional chromosome abnormalities were observed. In addition, after achieving remissions, they didn't revert to chronic phase of chronic myelogenous leukemia (CML) and showed normal neutrophil alkaline phosphatase scores, and the Ph1 chromosome disappeared completely in case 1 and coexisted with the normal chromosome in case 2. These findings suggest that diagnosis of both cases should not be CML blast crisis (BC) but Ph1 positive acute leukemia, and Ph1 positive AMLL may be a distinct clinical entity to be distinguished from CML-BC.
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PMID:[Philadelphia chromosome positive acute mixed lineage leukemia with bcr (M-BCR-1) rearrangement]. 215 95


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