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)

Conventional cytogenetic analysis (CCA) is the standard method for monitoring of the Philadelphia (Ph) chromosome in chronic myeloid leukemia (CML). Evaluation of breakpoint cluster region/abelson murine leukemia (BCR/ABL) fusion using interphase fluorescence in situ hybridization on peripheral blood smears (PB-FISH) might be another approach allowing more frequent and less invasive follow-up investigations. Herein, BCR/ABL fusion gene was assessed on 21 PB smears from 16 CML patients in chronic phase. Results of PB-FISH were compared with those of CCA and interphase FISH on bone marrow aspirates (BM-FISH). PB-FISH analysis was combined with CD3 immunophenotyping that allowed simultaneous investigation of the leukemic status of CD3(+) T lymphocytes and scoring CD3(-) cells for BCR/ABL fusion gene. Moreover, the frequency of BCR/ABL fusion in nonlymphoid PB cells was estimated according to the differential leukocyte counts. The incidence of BCR/ABL(+) fusion signals in CD3(+) T cells of CML patients was 5.3% (SD +/- 1.9) and did not exceed the normal cut-off value of 8%. A significant correlation (P < 0.001) was found between results of PB-FISH and methods of BM analysis (CCA or BM-FISH). Correction of PB-FISH results to include only nonlymphoid or CD3(-) cells reduced the mean of differences and improved agreement between PB-FISH and CCA or BM-FISH methods. The best agreement was noted between CCA and PB-FISH on nonlymphoid cells. On the other hand, results of BM-FISH agreed well with those of PB-FISH on CD3(-) cells. These findings imply that PB-FISH on nonlymphoid or CD3(-) cells is reliable and may replace BM analysis for monitoring of response to treatment in CML patients.
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PMID:Efficiency of interphase fluorescence in situ hybridization for BCR/ABL on peripheral blood smears for monitoring of CML patients: a comparison with bone marrow findings. 1245 17

The BCR/ABL tyrosine kinase inhibitor imatinib mesylate (Gleevec, STI571; Novartis, Basel, Switzerland) has shown remarkable efficacy in the treatment of chronic myelogenous leukemia (CML), with a high proportion of patients achieving complete cytogenetic responses (CCRs). However, it is not clear whether remissions will be durable and whether imatinib mesylate can eliminate the malignant primitive progenitors in which the disease arises. We investigated whether residual BCR/ABL+ hematopoietic progenitors were present in patients who achieved CCRs with imatinib mesylate treatment. CD34+ progenitor cells were selected from bone marrow mononuclear cells (MNCs) and analyzed for the presence of the BCR/ABL fusion gene by fluorescence in situ hybridization (FISH). CD34+ cells were also plated in committed progenitor (colony-forming cell, or CFC) and primitive progenitor (long-term bone marrow culture-initiating cell, or LTCIC) cultures and resulting colonies analyzed for the presence of BCR/ABL+ cells by FISH. Using these assays, residual BCR/ABL+ progenitors were detected in all patients studied. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated increased levels of BCR/ABL mRNA in CD34+ cells compared with total MNCs. Evaluation of samples collected at different time points demonstrated persistence of BCR/ABL+ progenitors despite continued treatment with imatinib mesylate. Our results indicate that inhibition of BCR/ABL tyrosine kinase activity by imatinib mesylate does not eliminate malignant primitive progenitors in CML patients. Patients in CCR with imatinib mesylate treatment need to be followed carefully to assess for risk of relapse.
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PMID:Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment. 1257 34

Three new cases are reported of cytogenetically Philadelphia-negative (Ph-) chronic myelocytic leukemia (CML), with positive BCR/ABL gene rearrangement according to a reverse transcriptase polymerase chain reaction technique. Fluorescence in situ hybridization (FISH) studies using different probes showed three different situations involving chromosomes 9 and 22 for the masked BCR/ABL fusion gene. With the use of BCR/ABL-extra signal and CEP 9 probes (Vysis, Downers Grove, IL, USA), FISH studies detected the BCR/ABL fusion gene at the end of chromosome 9 in patient 1, a BCR/ABL fusion gene on both chromosomes 22 in patient 2 (who was in an accelerated phase of CML), and a BCR/ABL fusion signal on chromosome 22 in patient 3. Interestingly, FISH interphase signals showed the same pattern in patients 1 and 3, but the BCR/ABL fusion gene was located on different chromosomes. Careful interpretation of the results and a simultaneous study of nuclei and metaphases are therefore recommended in each case. In conclusion, in cases of Ph- CML, FISH studies are of paramount importance since they can detect chromosomal reorganization and its location, and can also provide quantitative follow-up of these patients.
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PMID:Chimeric BCR/ABL gene detected by fluorescence in situ hybridization in three new cases of Philadelphia chromosome-negative chronic myelocytic leukemia. 1260 28

PCR for the BCR/ABL fusion transcript provides a highly sensitive and specific method for detecting minimal residual disease in patients with chronic myeloid leukemia (CML). We sought to determine if quantitative PCR measurement of peripheral blood BCR/ABL transcript can be used to monitor response in CML patients with clinically evident disease while receiving the protein tyrosine kinase inhibitor STI-571. Serial bone marrow cytogenetics and peripheral blood BCR/ABL mRNA levels were measured in 17 patients [9 with chronic phase (CP) and 8 with accelerated phase or blast crisis (AP/BC)] during 1 year of treatment. Overall, quantitative PCR BCR/ABL transcript level decreased by a median of 0.9 log during the first 3 months, and by 1.6 logs by 12 months. Among cytogenetic responders (6 CP and 2 AP/BC), median BCR/ABL copy number was 0.9 and 2.1 logs lower than baseline after 3 and 12 months of treatment, respectively. No patient became PCR-negative for BCR/ABL. Among cytogenetic non-responders, BCR/ABL transcript level decreased by 0.4 logs after 3 months, with no subsequent reductions. At study entry, BCR/ABL expression in cytogenetic responders and non-responders was similar. However, BCR/ABL expression became significantly different 3 months after treatment (p = 0.02), and increasingly different with continued therapy (p = 0.04, 0.005, 0.0008 at 6, 9 and 12 months, respectively). Our results demonstrate that PBMC BCR/ABL mRNA levels correlate well with response to STI-571. This non-invasive, rapid and sensitive PCR-based assay can be used to monitor response to STI-571.
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PMID:Quantitative monitoring of BCR/ABL transcript during STI-571 therapy. 1261 14

We present a 28-year-old patient with chronic myeloid leukemia (CML) in chronic phase complicated with nephrotic syndrome. The bone marrow cells revealed the presence of Philadelphia chromosome, the cytogenetic hallmark of CML, that results from a balanced, reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11). This reciprocal translocation leads to the formation of the BCR/ABL fusion gene, the presence of which was confirmed using the highly sensitive fluorescence in situ hybridization technique. The renal biopsy was compatible with minimal change nephrotic syndrome. To the best of our knowledge, this is the first case of minimal change nephrotic syndrome associated with CML before the administration of any therapy.
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PMID:A case of chronic myeloid leukemia complicated with minimal change nephrotic syndrome. 1262 95

We describe a patient initially diagnosed with a chronic myeloproliferative disorder in the accelerated phase. Cytogenetic analysis showed the presence of two independent clones. One clone contained a typical Philadelphia (Ph) chromosome due to t(9;22)(q34;q11), as the sole abnormality which was proven molecularly to result in the b2a2-BCR/ABL fusion. The other clone displayed a complex karyotype with several structural and numerical aberrations including trisomy 11 and 22 but lacking a t(9;22) or any other structural abnormalities involving chromosomes 9 and 22. Fluorescence in situ hybridization demonstrated that the t(9;22) was present only in cells with two copies of chromosomes 11 and 22. In contrast, cells with trisomies 11 and 22 lacked evidence for a BCR/ABL fusion. Based on the genetic findings, simultaneous chronic and acute myelocytic leukemias were diagnosed rather than a blastic phase of a chronic myelocytic leukemia.
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PMID:Cytogenetic and molecular characterization of simultaneous chronic and acute myelocytic leukemia. 1266 40

Although the chronic phase of chronic myelocytic leukemia (CML) is characterized by the Philadelphia (Ph) chromosome creating a hybrid BCR/ABL gene, additional genetic changes involved in blast crisis are poorly understood. We report a 4-8-fold amplification by tandem duplication of the BCR/ABL fusion gene clustered on a masked Ph chromosome in a 61-year-old male patient with CML in myeloblastic crisis. Our finding suggests that the BCR/ABL amplification may play a role as a novel mechanism in the progression to an aggressive blast transformation in some cases of Ph-positive CML.
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PMID:Amplification of the BCR/ABL fusion gene clustered on a masked Philadelphia chromosome in a patient with myeloblastic crisis of chronic myelocytic leukemia. 1278 48

Chronic myelogenous leukemia is a myeloproliferative disorder (MPD) that, over time, progresses to acute leukemia. Both processes are closely associated with the t(9;22) chromosomal translocation that creates the BCR/ABL fusion gene in hematopoietic stem cells (HSCs) and their progeny. Chronic myelogenous leukemia is therefore classified as an HSC disorder in which a clone of multipotent HSCs is likely to be malignantly transformed, although direct evidence for malignant t(9;22)+ HSCs is lacking. To test whether HSC malignancy is required, we generated hMRP8p210BCR/ABL transgenic mice in which expression of BCR/ABL is absent in HSCs and targeted exclusively to myeloid progenitors and their myelomonocytic progeny. Four of 13 BCR/ABL transgenic founders developed a chronic MPD, but only one progressed to blast crisis. To address whether additional oncogenic events are required for progression to acute disease, we crossed hMRP8p210BCR/ABL mice to apoptosis-resistant hMRP8BCL-2 mice. Of 18 double-transgenic animals, 9 developed acute myeloid leukemias that were transplantable to wild-type recipients. Taken together, these data indicate that a MPD can arise in mice without expression of BCR/ABL in HSCs and that additional mutations inhibiting programmed cell death may be critical in the transition of this disease to blast-crisis leukemia.
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PMID:Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias. 1289 Aug 67

Chronic myeloid leukemia (CML) is a clonal neoplastic disorder, characterized by t(9;22)(q34;q11) that results in the formation of the Philadelphia chromosome (Ph) and the BCR/ABL fusion gene. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for CML. Much of its therapeutic efficacy is attributed to a graft-versus-leukemia (GVL) effect exerted by donor-derived lymphoid cells against the Ph positive (Ph+) clone. Post-HSCT monitoring by cytogenetic and molecular detection of the Ph+ clone is necessary, so that pre-emptive immunologic or pharmacologic treatment may be administered at an early stage of relapse. However, under rare circumstances a second Ph negative (Ph-) leukemia may evolve post-HSCT. The pathogenetic possibilities included leukemia arising from donor-derived hematopoietic stem cells (HSCs), or transformation of residual recipient-derived Ph- HSCs that have survived the conditioning chemotherapy and radiotherapy. Recipient-derived Ph- leukemia may be related to genetic alterations that precede the onset of CML, or myelotoxic effects of the HSCT conditioning regimen. The diagnosis of Ph- relapses requires detailed investigations by conventional karyotyping, fluorescence in-situ hybridization (FISH), and molecular analysis; as well as chimerism studies that help to document the donor or recipient origin of the leukemia. Although uncommonly reported in the past, Ph- relapses may in fact be more frequent if leukemic relapses post-HSCT are more thoroughly evaluated with these investigations. The recognition of Ph- relapses are important in several ways. Ph- relapses cannot be identified by monitoring investigations targeting the Ph+ clone, so that the early detection of Ph- leukemia is usually not possible. Furthermore, Ph- relapses will not respond to therapeutic strategies effective against the Ph+ CML clone.
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PMID:The occurrence of Philadelphia chromosome (Ph) negative leukemia after hematopoietic stem cell transplantation for Ph positive chronic myeloid leukemia: implications for disease monitoring and treatment. 1291 63

In this study we present the applicability of fluorescence in situ hybridisation (FISH) and RT-PCR to detect the minimal residual disease (MRD) in relapsed Ph+ children after donor lymphocyte infusion (DLI) post bone marrow transplantation (BMT). In both patients BCR/ABL fusion was detected and its transcript at the moment of relapse. After the DLI treatment in short time intervals a decreasing number of cells with BCR/ABL fusion were noticed and the expression of the hybrid gene disappeared. These results demonstrate that all the methods presented in this study provide a feasible, rapid and accurate way for the detecting of the minimal residual disease after DLI in Ph positive CML patients.
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PMID:Molecular follow up of donor lymphocyte infusion in CML children after allogeneic bone marrow transplantation. 1456 29


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