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

Twenty six patients with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia (CML) treated with IFN-alpha were classified on the basis of the fusion pattern of BCR/ABL chimeric mRNA determined by a reverse-transcriptase-polymerase chain reaction (RT-PCR) method. The relationship between the fusion pattern of BCR/ABL mRNA and the clinical outcome was also analysed. Twelve patients showed M-bcr exon 3/ABL exon 2 (B3/A2) chimeric mRNA and nine had M-bcr exon 2/ABL exon 2 (B2/A2) mRNA. Eleven of the 12 patients with B3/A2 achieved complete hematological response with IFN-alpha therapy, as did three of the nine patients with B2/A2. The mean duration to blastic crisis was significantly longer in the B3/A2 patients (mean 52.4 months) than in the B2/A2 patients (mean 26.2 months) (p less than 0.01). These results suggest that the fusion pattern of BCR/ABL mRNA may affect the therapeutic response to IFN-alpha and clinical outcome in CML patients.
Leukemia 1992 Sep
PMID:Possible correlation between fusion pattern of BCR/ABL mRNA and clinical response to alpha-interferon in chronic myelogenous leukemia. 151 6

We report the biological characteristics of leukaemic blasts from two cases of acute leukaemia with an interstitial deletion of the long arm of chromosome 9 (9q-). Case 1 (FAB: M1) showed del(9)(q12q22) as the sole karyotypic anomaly, and case 2 (FAB: M1) presented del(9) (q12q22) in association with trisomy 10. In both cases, leukaemic blasts presented unique cytological features, such as prominent vacuoles on Giemsa staining, or strong localization of myeloperoxidase resembling 'pseudo-Chediak-Higashi' granules. Immunophenotyping of blasts revealed the biphenotypic expression of T-lymphoid/myeloid antigens (CD2, CD7/CD33) in addition to CD34. Neither T-cell receptor beta (TCRB), T-cell receptor gamma (TCRG) nor Ig heavy chain (IGH) genes were clonally rearranged. Furthermore, there was neither rearrangement nor expression of ABL, which is located at 9q34, indicating that the deletion involved bands centrometric to 9q34 did not induce the activation of ABL. DNA synthesis of the blasts was stimulated (stimulation index greater than 2.0) in the presence of interleukin (IL)-3, IL-4, granulocyte colony-stimulating factor or erythropoietin (Epo). IL-3 and IL-4 could also support the in vitro growth of leukaemic blast colonies, and the IL-3- or IL-4-dependent blast colony growth was synergistically enhanced by the addition of IL-6 or Epo. These observations imply that T-lymphoid/myeloid or pluripotent stem cells may be closely involved in the development of 9q- AML.
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PMID:Interstitial 9q deletion in T-lymphoid/myeloid biphenotypic leukaemia. 155 Jul 72

ABL-MYC, a murine retrovirus that encodes the v-abl and c-myc oncogenes, was constructed from Abelson murine leukemia virus (A-MuLV) in order to assess the biological consequences of co-expression of these genes in lymphoid cells. When inoculated into mice this retrovirus induced plasmacytomas in up to 100% of infected mice and less frequently induced pre-B lymphomas. Both tumor types contained genome-length proviruses in one or a few chromosomal locations, were mono- or oligoclonal as judged by immunoglobulin gene rearrangement and had unrearranged endogenous c-myc loci. The type of tumor induced depended upon the age and strain of mouse, and whether helper virus was present in the inoculated virus pool. ABL-MYC induced plasmacytomas with or without helper virus, with or without pretreatment of the mice with pristane, and in strains of mice resistant to pristane-induced plasmacytomas. Pristane treatment prior to ABL-MYC infection shortened the latent period of plasmacytomagenesis and produced mostly IgM-secreting tumors rather than IgA-secreting tumors, which predominantly arose in the absence of pristane. Control viruses for ABL-MYC with either a deletion in v-abl or a frameshift mutation in c-myc caused predominantly monocyte/macrophage tumors and pre-B-cell lymphomas respectively. Histopathological analysis of ABL-MYC-infected mice showed foci of transformed plasma cells as early as 14 days after infection. These results indicate that v-abl and c-myc act synergistically to transform mature B cells with high efficiency.
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PMID:A retrovirus that expresses v-abl and c-myc oncogenes rapidly induces plasmacytomas. 156 79

The Philadelphia (Ph) chromosome can be detected in the vast majority of patients with chronic myelogenous leukemia (CML). We performed a long-range analysis of chromosomal translocation junction by pulsed-field gel electrophoresis (PFGE) techniques, to examine whether molecular evidence of a reciprocal Ph translocation exists in Ph-positive CML as well as Ph-negative, M-BCR rearrangement-positive CML. The rearrangement within M-BCR and ABL was detected in all patients including nine Ph-positive CML, and three Ph-negative CML. The rearranged 3'-abl fragments showed comigration with rearranged 5'-bcr fragment in rare-cutting restriction enzyme digests in all patients with Ph-positive CML. Thus, the physical linkage of the 3' part of ABL to the 5' side of M-BCR on 22q-chromosome was shown. The same linkage was also demonstrated in all three patients with Ph-negative CML. Meanwhile, the rearranged 3'-bcr fragments showed comigration with rearranged pHabl5' (or T39-1-2) fragments in all patients with Ph-positive CML, indicating the linkage of the 5' end of ABL to the 3' part of M-BCR on 9q+ chromosome. However, this linkage was absent in two Ph-negative CML patients who could be studied. The results suggest that a genomic insertion of 3' ABL into M-BCR in Ph-negative CML occurs by a single cytogenetic event rather than a two-translocation mechanism.
Leukemia 1992 May
PMID:Absence in Ph-negative, M-BCR rearrangement-positive chronic myelogenous leukemia of linkage between 5' ABL and 3' M-BCR sequences in Philadelphia translocation. 159 4

The Philadelphia (Ph) translocation is the most common cytogenetic abnormality in adult acute lymphoblastic leukemia (ALL) and is associated with an adverse prognosis. Using polymerase chain reaction (PCR) technology we recently observed a remarkably high incidence (55%) of BCR-ABL rearrangements in adult common ALL patients. In the present study we asked whether a subset of Ph-negative cALL, similarly to Ph-negative chronic myelocytic leukemia (CML) patients, exhibit BCR-ABL transcripts. PCR analysis of 58 adult Ph-negative cALL patients, including 47 cases with a normal karyotype revealed no evidence of chimeric BCR-ABL genes. We conclude that Ph-negative BCR/ABL-positive ALL is very rare entity if existing at all.
Leukemia 1992 May
PMID:Polymerase chain reaction analysis of BCR-ABL sequences in adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. 159 11

Therapy with interferon-alpha results in complete cytogenetic remission in 15-20% of patients with chronic myelogenous leukemia. Even during prolonged clinical follow-up, most of these patients do not relapse. However, because of the limited sensitivity of cytogenetic techniques (approximately 5%) and Southern blots (approximately 1%), it is uncertain whether the residual malignant clone becomes extinct or persists below the limit of detection in these patients. We used polymerase chain reaction to amplify the chimeric BCR-ABL transcripts in 18 patients with chronic myelogenous leukemia who became Ph1 chromosome negative while receiving treatment with interferon-alpha, either alone or in combination with interferon-gamma. At the time of study, these patients had been Ph1-negative for a median of 22+ months. Fifteen patients were positive for residual BCR-ABL transcripts. No residual BCR-ABL message was detected on analysis of multiple serial samples in three patients. In order to confirm these results, the samples from these three patients, along with positive and negative controls, were analyzed by two independent laboratories in a blinded fashion. In the first laboratory, RNA specimens from all three patients were considered negative using chemiluminescent acidinium-ester-labeled probes. In the second laboratory, samples from all three patients were also negative by conventional polymerase chain reaction (PCR). However, when a second round of amplification was carried out on the amplified samples using a different combination of primers, samples from two of the three patients were positive. The results confirm the presence of a small proportion of BCR-ABL-positive cells in the majority of patients who are in complete remission and highlight some of the potential problems of PCR-based analysis. There is a need to standardize PCR methodology and potential confounding factors need to be addressed before PCR can be generally applied to analysis of minimal residual disease in CML. The implications of BCR-ABL positivity for these patients are discussed.
Leukemia 1992 Aug
PMID:Minimal residual disease in interferon-treated chronic myelogenous leukemia: results and pitfalls of analysis based on polymerase chain reaction. 164 Jul 25

Pulsed field gel electrophoresis was used to construct a long-range map of the normal BCR gene. A single BssHII restriction fragment encompasses all the known exons of the BCR gene (except a small 5' part of exon one). MIuI has one restriction site within the first intron of the BCR gene and another 250 kb downstream. This MIuI fragment contains most of the BCR gene coding sequences apart from the first exon and contains more sequences downstream of the BCR gene than the BssHII fragment. The NarI restriction sites are very close to the BssHII sites in the BCR gene, but they differ in the ABL gene, so that NarI digests could theoretically provide additional information in chronic myeloid leukaemia (CML) patients. This map was used to confirm BCR gene involvement in two CML patients in whom results of conventional Southern blotting of DNA were ambiguous. It was also used in a third patient to demonstrate the presence of a breakpoint apparently outside the BCR gene. Preliminary evidence from the use of PFGE confirms the presence of three BCR-related genes homologous to 3' sequences in the classical BCR gene (BCR-1). These BCR-related genes are located at a considerable distance from BCR-1.
Leukemia 1991 Jul
PMID:Long-range mapping of the normal BCR gene. 164 56

Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL) is most common in adults and is associated with poor prognosis. Since karyotypic identification of the Philadelphia translocation has been hampered by technical difficulties, we used the polymerase chain reaction (PCR) to look for the BCR-ABL rearrangement in stored samples from a selected group of 314 German ALL patients. BCR-ABL transcripts were found in 77 of 179 adults and were restricted to those with B-precursor leukaemias. 55% of adult common ALL patients had BCR-ABL and its presence correlated with poor overall survival and remission duration. Of 135 children with common ALL, 5 (6%) primary cases and 8 (17%) with recurrent neoplasias were PCR-positive. We recommend prospective evaluation of BCR-ABL analysis with PCR in patients with a B-precursor leukaemia.
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PMID:Detection of chimeric BCR-ABL genes in acute lymphoblastic leukaemia by the polymerase chain reaction. 168 8

The Philadelphia chromosome defines chronic myeloid leukemia, and is mostly based on a translocation t(9;22) with a typical BCR-ABL rearrangement which also occurs in so called atypical translocations. The transformation of chronic myeloid leukemia is associated with clonal evolution in 80% of cases. The appearance of an isochromosome 17q unequivocally heralds the onset of a myeloid type of blast crisis. Treatment of Ph-positive CML has still to be considered palliative except for allogeneic bone marrow transplantation. The Philadelphia chromosome is also found in about 20% of patients with acute lymphoblastic leukemia and in about 2% of patients with nonlymphoblastic leukemia. It is associated with a poor prognosis. Molecular and cytogenetic findings help differentiating between de novo acute leukemia and blast crisis of chronic myeloid leukemia.
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PMID:[Cytogenetic and clinical features of Philadelphia chromosome positive leukemias]. 170 14

The interactions between haemopoietic progenitor cells and marrow stromal cells that are essential for the regulation of normal haemopoiesis are defective in chronic phase chronic myeloid leukaemia (CML). The presence of primitive progenitor cells (blast colony-forming cells, Bl-CFC) in the blood of patients with CML is reflected by their reduced capacity to bind to marrow derived stromal layers in vitro. Whereas normal bone marrow Bl-CFC bind irreversibly to cultured stromal layers (and none are found in normal blood), the Bl-CFC in CML bind transiently and then detach. The normal cell adhesion mechanism is partially sensitive to treatment with phosphatidylinositol-specific phospholipase C (Pl-PLC), indicating the participation of a phosphatidylinositol (Pl)-linked structure; however, when CML cells were treated with Pl-PLC it had no effect on progenitor binding. Two other Pl-linked structures, decay-accelerating factor (DAF) and lymphocyte function associated antigen-3 (LFA-3) were normally expressed on CD34 positive CML cells and normally susceptible to Pl-PLC treatment. The treatment of normal cells with Pl-PLC, to mimic the situation in CML, resulted in the indiscriminate and inefficient binding of Bl-CFC to stroma. Moreover, treatment of the normal cells with 5637 conditioned medium (CM), which contains haemopoietic growth factors, also reduced the binding capacity of normal Bl-CFC; 5637CM treatment did not alter the expression of DAF. It is proposed that a Pl-linked cell adhesion molecule (CAM) is deficient in CML as a consequence of the constitutive activation of ABL kinase whilst, in normal cells, CAMs attached in this manner are responsible for efficient adhesion to stroma and are regulated by growth factors.
Leukemia 1991 Aug
PMID:Deficiency of a phosphatidylinositol-anchored cell adhesion molecule influences haemopoietic progenitor binding to marrow stroma in chronic myeloid leukaemia. 171 60


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