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

The Philadelphia chromosome (Ph) is the cytogenetic hallmark of chronic myeloid leukaemia (CML) and is used to confirm the diagnosis of CML based on clinical and morphological criteria. We investigated 14 patients with features of CML but without detectable Ph chromosome. In seven patients, referred to as BCR+, M-bcr/abl rearrangement was detected by polymerase chain reaction (PCR). The seven remaining patients did not have M-bcr/abl rearrangement and are described as BCR-. BCR- patients were younger, had lower white blood cell counts (WBC) and lower basophilia. Four BCR- and four BCR+ patients underwent blastic transformation (BT). Response to therapy was fairly similar in both populations. According to French-American-British (FAB) Cooperative Leukaemia Group guidelines, all BCR- patients were classified as having classic form CML or 'chronic granulocytic leukaemia' (CGL) when based only on morphological data. This study further confirms the existence of true CML cases without Ph chromosome or M-bcr/abl rearrangement and shows that this entity differs only slightly from classic form Ph+ CML. The Ph-BCR- subgroup raises two problems. First, the differential diagnosis with atypical CML or CMML, based on morphological data, and secondly, the therapeutic follow-up in the absence of a specific marker. In contrast, the residual disease of Ph-BCR- patients can be monitored by PCR. More advanced molecular and biochemical techniques will be required to understand which molecular mechanisms underlie Ph-BCR- CML, resulting in phenotypes sometimes indistinguishable from Ph+ CML.
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PMID:Philadelphia chromosome-negative chronic myeloid leukaemia: a report of 14 new cases. 779 55

A patient with accelerating Ph+ve chronic granulocytic leukaemia (CGL) was considered for autologous BMT using marrow 'purged' by 4 weeks long-term culture (LTC). Efficacy of purging was determined using reverse transcriptase PCR for BCR-ABL mRNA transcripts b2a2 and b3a2. Peripheral blood and bone marrow were compared. Three observations emerged: (i) the initial b2a2:b3a2 ratios for unmanipulated blood and marrow were different with values of 9:1 and 2:1 respectively; (ii) both transcripts were successfully 'purged' with LTC of blood but not marrow; and (iii) LTC of marrow caused a transient increase in relative levels of b3a2 mRNA and a corresponding reduction in the b2a2 signal. This is the first case where such differences have been demonstrated in association with LTC.
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PMID:Long-term culture and molecular biological studies highlight differences in relative BCR-ABL expression levels in the peripheral blood and bone marrow of a patient with chronic granulocytic leukaemia. 780 92

In human leukemia, activation of the ABL proto-oncogene locus on chromosome 9 most commonly occurs as a result of its fusion to the BCR locus on chromosome 22. The resulting chimeric protein displays an elevated tyrosine kinase activity. We have identified a novel activation of ABL which involves a gene located on chromosome 12, designated TEL. Like BCR, TEL is fused in-frame with ABL and produces a fusion protein with an elevated tyrosine kinase activity when assayed in an immune complex. The amino-terminal sequences of TEL encode a helix-loop-helix motif which may mediate dimerization.
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PMID:The novel activation of ABL by fusion to an ets-related gene, TEL. 780 37

A subset of adult acute lymphoblastic leukemia (ALL) patients have blast cells which co-express myeloid-associated antigens (MY+ ALL). We have analyzed 113 adult ALL cases for expression of MY-associated antigens (MAA). ALL was diagnosed by standard morphology, cytochemistry, and immunophenotype in central review. MY+ ALL was diagnosed when > or = 20% of lymphoblasts co-expressed CD13 and/or CD33. Overall incidence of MY+ was 31/113 (27%). MAA expression was not significantly correlated with WBC, blast count, hemoglobin, or hematocrit. MY+ cases were more likely to express B-associated antigens, especially CALLA, and to be FAB L2, Ph+, or to have the BCR-ABL translocation by PCR, but these differences were not statistically significant. All patients were induced with a L10M regimen, and 67 (59%) achieved CR: 43/66 (65%) of B MY neg; 14/29 (48%) of B MY+; 10/16 (63%) T MY neg; and 0/2 T MY+. In age-adjusted analyses CR rate did not differ significantly between MY+ and MY neg patients or between B- and T-cell patients. Of the 113 patients, 84 have died and the remaining 29 patients have been followed for a median of 49 months. In proportional hazards regression analyses adjusting for age and WBC, heterogeneity of survival among the four groups was statistically significant (p = 0.021), largely due to MY status. The mortality rate was 85% greater for MY+ patients compared to MY neg patients (two-tailed p = 0.013). By contrast, survival did not vary significantly between B- and T-cell patients. The data indicate that MAA expression is useful for predicting overall survival of adult patients with ALL treated in a L10M protocol. As a predictive factor MAA expression is comparable to the WBC and superior to the more standard stratification by B- or T-cell markers for this group of patients.
Leukemia 1994 Dec
PMID:Expression of myeloid antigens by blast cells in acute lymphoblastic leukemia of adults. The Southwest Oncology Group experience. 780 99

CML patients possess either a b3-a2 or a b2-a2 fusion between the BCR and ABL genes. Depending on the type of fusion, two different series of non-self potentially immunogenic peptides may be produced. If they are presented by HLA class I molecules and recognized by cytotoxic CD8 lymphocytes, individuals could be more susceptible or resistant to leukemic cells bearing one or the other form of fusion according to their HLA class I phenotype. To test this point, the frequencies of HLA-A and HLA-B alleles were compared between b3-a2 and the b2-a2 CML patients. In essence, no difference was found whose significance could withstand correction for multiple comparisons.
Leukemia 1994 Dec
PMID:The HLA class I-CML association revisited taking into account the two forms of gene fusion in the Philadelphia chromosome. A multicenter study. 780 1

The Philadelphia translocation commonly observed in chronic myeloid leukaemia (CML) and a proportion of cases of acute leukaemia results in the creation of a chimeric fusion protein, BCR-ABL. The fusion protein exhibits an elevated tyrosine kinase activity as compared to normal ABL. Using a temperature sensitive mutant of p210 BCR-ABL (ts-p210) we find that the primary effect of BCR-ABL expression in an IL-3 dependent cell line is to prolong survival following growth factor withdrawal; only a small proportion of cells remain viable and rapidly evolve to complete growth factor independence. During passage in the presence of IL-3 at the temperature permissive for kinase activity, ts-p210 expressing cultures become dominated by completely growth factor independent cells within 10-30 days. There is also a significant difference between BCR-ABL and IL-3 mediated signalling with respect to the MAP kinase pathway; in contrast to IL-3 stimulation or v-ABL expression, BCR-ABL does not signal ERK 2 (MAP 2 kinase) activation, underlining the apparent inability of BCR-ABL to deliver an immediate proliferative signal in Ba/F3 cells. Our data suggest that growth factor independence does not simply reflect the convergence of BCR-ABL and IL-3 mediated signalling pathways and its development, at least in Ba/F3 cells, requires prolonged exposure to BCR-ABL kinase activity. We suggest that the myeloid expansion characteristic of CML may result from the prolongation of survival of myeloid progenitor cells under conditions of limiting growth factor rather than their uncontrolled proliferation.
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PMID:A temperature sensitive p210 BCR-ABL mutant defines the primary consequences of BCR-ABL tyrosine kinase expression in growth factor dependent cells. 781 29

Chronic myeloid leukemia is a disease marked by expanded clonal hematopoiesis; it is incurable by chemotherapy or radiation but is cured in a majority of patients receiving bone marrow transplantation from nonidentical sibling donors, an outcome generally attributed to a T cell-mediated graft-versus-leukemia effect. In this report, we examine the effect of the P210BCR-ABL fusion protein of the BCR-ABL oncogene, the molecular hallmark of chronic myelogenous leukemia, on the sensitivity of mouse cell lines to apoptosis induced by chemotherapy, radiation, or activated cytotoxic T lymphocytes (CTLs). We find that, although cells expressing P210BCR-ABL by gene transfer are more resistant than their normal counterparts to apoptosis induced by chemotherapy or radiation, they are equally susceptible to apoptosis induced by alloreactive CTLs. These results show that CTLs overcome BCR-ABL-mediated resistance to apoptosis and, therefore, provide a biological correlation for the success of allogeneic bone marrow transplantation in chronic myelogenous leukemia.
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PMID:Cytotoxic T cells overcome BCR-ABL-mediated resistance to apoptosis. 783 7

The bcr-abl oncogene is a fusion gene resulting from a reciprocal translocation which forms the hallmark of chronic myeloid leukemia (CML). Antisense oligonucleotides complementary to the two possible mRNA breakpoints were found to inhibit cell growth of CML patient cells and cell lines, but doubt exists about their specificity. In order to test the specificity, phosphorothioate and 3' phosphorothioate capped antisense BCR-ABL oligonucleotides of different length were used. Stability, cellular uptake of oligonucleotides and effect on cell growth were studied in two CML cell lines, BV173 and LAMA-84. Phosphorothioate antisense BCR-ABL oligonucleotides were most stable, showed the highest uptake and induced cell death in BV173 but not in LAMA-84 cells. We selected the most effective antisense oligonucleotide for further analysis. The BV173 and LAMA-84 cell lines do not express the normal c-abl protein, we therefore used a c-abl specific monoclonal antibody for the detection of p210bcr-abl expression by flow cytometry. Dead cells found after treatment were gated out of analysis. Although BCR-ABL antisense oligonucleotides can induce apoptosis, no reduction of p210bcr-abl levels could be detected in living cells after treatment with antisense oligonucleotides. We conclude that antisense mediated inhibition of translation of mRNA into p210bcr-abl is not the mechanism responsible for the induction of apoptosis in cell line BV173.
Leukemia 1995 Jan
PMID:Phosphorothioate BCR-ABL antisense oligonucleotides induce cell death, but fail to reduce cellular bcr-abl protein levels. 784 6

The clinical status of a homogeneous cohort of long-term survivors of allogeneic marrow transplantation was assessed and residual leukaemia was studied by reverse transcription polymerase chain reaction for leukaemia specific BCR-ABL mRNA. The group comprised 34 consecutive patients with CML in chronic phase treated by chemoradiotherapy and transplantation of bone marrow from HLA-identical sibling donors between February 1981 and December 1983 in the joint Hammersmith-Northwick Park programme. The probability of survival at 10 years was 59 +/- 17%. Eighteen of the 19 surviving (95%) patients have Karnofsky scores of 90 or 100% indicative of a good performance status. One of the survivors had evidence of relapse 6.5 years after transplant but has since been restored to complete remission by treatment with interferon-alpha followed by donor leucocyte transfusions. Surprisingly, 2 of the 19 patients who have been in remission for over 10 years have molecular evidence of persisting leukaemic cells. Quantification by competitive PCR indicated that the malignant clone persisted at low levels. The data suggest that the majority of long-term survivors after BMT for CML are in good health and may be regarded as cured. Some long-term survivors, however, may still harbour residual leukaemic cells and continued monitoring for late relapse is warranted. Late relapse is amenable to further therapy with leukocyte transfusions from the original marrow donor.
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PMID:Detection of residual leukaemia more than 10 years after allogeneic bone marrow transplantation for chronic myelogenous leukaemia. 785 36

A 49 year-old man was admitted to our hospital in May 1989, with a cervical tumor and leukocytosis. He had been pointed out leukocytosis for last two years. Peripheral blood examinations demonstrated an increase of leukocytes (39,500/microliters) with low neutrophil alkaline phosphatase, eosinophilia and immature cells. Examination of bone marrow revealed normoplasia with 5.6% eosinophils, 1.4% myeloblasts, 2.6% promyelocytes and 250/microliters megakaryocytes. Cytogenetic analysis disclosed 46, XY, t (12;13) (p13;q12). Southern blot analysis showed no BCR rearrangement. The tumor cells had infiltrated the lymph nodes. Pathological finding agreed with the specimen of the lymph node as in the clot section of bone marrow. He was diagnosed as having a chronic myeloproliferative disorder with tumor formation and was treated with anti-leukemia drugs, including BH-AC, THP, VDS, MTX, VP-16, BUS, 6MP and uvenimex. He showed hematological remission, temporary, but he did not reach cytogenetical remission and died in April 1990. Further study in a large series is necessary to define whether the abnormality of the chromosome with t(12;13) (p13;q12) is characteristic in cases with tumor formation.
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PMID:[Atypical chronic myeloproliferative disorder with translocation (12;13) (p13;q12) and tumor formation]. 786 15


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