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)

Diffuse large B-cell lymphoma (DLBCL) accounts for 30-40% of all adult non-Hodgkin's lymphomas, yet the understanding of its underlying genetic abnormalities remains poor. Our present study used the serological analysis of recombinant cDNA expression libraries (SEREX) technique to identify DLBCL-associated antigens. SEREX screening of testis libraries has previously identified cancer-testis antigens (CTAs) that may act as disease-specific targets for immunotherapy. Screening a testis cDNA expression library with serum from a DLBCL patient identified a total of 94 positive clones, representing 28 distinct antigens. Two of these antigens were novel, 8 were previously uncharacterised, and the remainder were proteins of known function. Screening of the antigens with sera from DLBCL (n = 10), acute myeloid leukaemia (AML, n = 10) and chronic myeloid leukaemia (CML, n = 10) patients, alongside normal healthy donor controls (n = 20), revealed that 7 of the antigens were recognised by DLBCL sera but not normal donor sera, whilst 2 of these antigens were also recognised by leukaemic sera. Some of the genes identified here were already known to be transcribed in DLBCL. The mRNA expression of the majority of the remaining antigens was confirmed in DLBCL cell lines using reverse-transcriptase PCR (RT-PCR). Our study identified a number of DLBCL associated antigens that may be suitable as prognostic/diagnostic markers and/or for the immunotherapy of haematologic malignancies.
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PMID:Serologic detection of diffuse large B-cell lymphoma-associated antigens. 1512 89

Residual disease in chronic myeloid leukemia patients may be assessed by various molecular methods. After imatinib treatment a significant proportion of patients achieve complete cytogenetic remission (CCR) and a sensitive method is necessary to monitor treatment response and to detect early signs of relapse. Reverse-transcriptase polymerase chain reaction (RT-PCR) is by far the most sensitive approach to assess residual disease in this group of patients. Qualitative PCR methods give only limited information about the residual leukemic mass. Quantitative RT-PCR (Q-PCR) assays enable to monitor the kinetics of residual BCR-ABL transcripts over time in patients with a good response to imatinib. Early Q-PCR results on imatinib treatment can help to identify individuals who are likely to have a good response. In chronic phase patients after CCR, Q-PCR may identify patients who are likely to continue with their CCR or to relapse and may help to optimize treatment for this group of patients. The definition of molecular surrogate endpoints beyond CCR for studies which are currently planned demands standardization of the nomenclature and of technologies to measure these targets.
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PMID:Molecular surveillance of chronic myeloid leukemia patients in the imatinib era - evaluation of response and resistance. 1517 8

Survival among chronic myelogenous leukemia (CML) patients can be linked to the reduction in leukemic cell burden. Treatment with imatinib mesylate results in a high frequency of complete cytogenetic response, which can be further stratified using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). We have serially monitored peripheral blood and bone marrow BCR-ABL transcripts using qRT-PCR in CML patients commencing imatinib therapy, and compared the results with bone marrow cytogenetics. Seventeen patients (aged 25-74 yr) with Philadelphia chromosome positive CML in first chronic phase were treated with imatinib targeting a dose of 400 mg/d. The median follow up is 30 mo (range 9-33 mo). Every third month the product of the BCR-ABL fusion gene was evaluated in both blood and bone marrow specimens by real-time RT-PCR using the TaqMan probe system. In 113 simultaneously obtained blood and bone marrow samples, the BCR-ABL transcript values agreed well with cytogenetic data. Blood and bone marrow specimens gave comparable values for BCR-ABL transcripts. Before start of imatinib therapy there was a considerable variation in BCR-ABL transcripts among the patients, ranging approximately one log (base 10). Similarly, patients with a complete cytogenetic response following imatinib therapy had variable BCR-ABL transcript levels, ranging at least three logs (base 10). The major decline in BCR-ABL transcripts occurred within 6 mo after start of imatinib therapy. The decline in BCR-ABL transcripts, following imatinib therapy, appears to level off at 12-15 mo. Two late responders were identified with a still decreasing level in BCR-ABL transcripts after 24 mo of treatment. It is concluded that BCR-ABL mRNA quantification in peripheral blood is suitable for routine monitoring of the response to treatment and long-term disease status in CML, especially in patients who have achieved a complete cytogenetic response. A plateau in BCR-ABL transcripts seems to have been reached after 12-15 mo of imatinib treatment; however, some "late responders" are seen.
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PMID:Serial monitoring of BCR-ABL transcripts in chronic myelogenous leukemia (CML) treated with imatinib mesylate. 1557 19

We describe the cytogenetic, fluorescence in situ hybridization (FISH), and molecular findings in a patient who developed a typical chronic lymphocytic leukemia (CLL) 20 months after the diagnosis of a Philadelphia (Ph)-positive chronic myeloid leukemia. Unstimulated bone marrow culture showed a 46,XX,t(9;22)(q34;q11) karyotype, and interphase FISH detected the presence of a BCR/ABL fusion signal in 13% of cells. On stimulated bone marrow culture, a normal karyotype and a 13q14 deletion by interphase FISH with D13S319 probe in 14% of the cells were found. Molecular studies detected the chimeric BCR/ABL messengers by nested reverse-transcriptase polymerase chain reaction. The B-cellular clone was documented by the presence of a clonal heavy chain immunoglobulin rearrangement. The coexistence of these two hematologic malignancies leads to questions about their cell(s) of origin. We provide evidence that CLL arose in a Ph-negative clone. The implications of these findings are discussed.
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PMID:Chronic lymphocytic leukemia developing in a patient with chronic myeloid leukemia: evidence of distinct lineage-associated genomic events. 1608 Sep 61

Kinase domain receptor (KDR) and Semaphorin3 (Sema3) have a functional relationship and are expressed in human bone marrow (BM). We cultured in vitro bone marrow stromal cells (BMSCs) and collected nonadherent cells from patients with acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) and normal individuals. Reverse transcriptase polymerase chain reaction enzyme-linked immunosorbent assay (RT-PCR-ELISA) was performed to examine KDR and Sema3 genes expression, using beta2 microglobulin as an internal reference. KDR expression ratio in normal control BMSCs (97.0%, 32/33) was higher than in its corresponding nonadherent cells (70.8%, 17/24). KDR expression levels in ALL BMSCs and AML nonadherent cells were significantly higher than in normal controls. Sema3 expression ratios in nonadherent cells from AML (78.6%, 11/14) and CML (71.4%, 10/14) were both significantly lower than in normal control (100%, 27/27), its expression levels were also significantly lower than in normal control. Sema3 expression level in normal BMSCs was significantly lower than in nonadherent cells. Sema3 and KDR genes expression levels displayed a significantly positive correlation in normal control and ALL nonadherent cells (r=0.703, P=0.002; r=0.999, P=0.001). These results suggests that KDR may play a critical role in sustaining the hematopoietic microenvironment due to its high expression, and that KDR may be involved in pathogenesis of AML and ALL. Sema3 could also sustain the survival of hematopoietic cells with its high expression, while Sema3 gene expression may be inhibited in AML and CML.
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PMID:KDR and Sema3 genes expression in bone marrow stromal cells and hematopoietic cells from leukemia patients and normal individuals. 1608 43

The unique molecular characteristic of chronic myeloid leukemia (CML), the disease-causing ABL (9q34) to BCR (22q11) translocation, has provided an invaluable tool for disease diagnosis and monitoring of treatment response. The traditional standard in this regard is bone marrow karyotype, also known as conventional cytogenetics (CC), which reveals a shortened chromosome 22, the Philadelphia chromosome, t(9;22)(q34;q11). CC in CML has also been effectively used for monitoring the response to drug therapy. However, this particular laboratory test misses submicroscopic BCR/ABL translocations and is suboptimal for minimal residual disease (MRD) assessment. Both fluorescence in situ hybridization (FISH) and reverse-transcriptase polymerase chain reaction (RT-PCR) feature higher sensitivity in terms of both diagnosis and MRD assessment in CML, compared to CC. Another advantage of these alternative tests is their effective applicability to peripheral blood specimens. The current review highlights the practical literature with respect to the use of FISH for CML whereas the use of RT-PCR has been extensively covered in recent communications.
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PMID:Fluorescent in situ hybridization in the diagnosis, prognosis, and treatment monitoring of chronic myeloid leukemia. 1639 61

Imatinib mesylate (STI571), a specific Bcr-Abl inhibitor, has shown a potent antileukemic activity in clinical studies of chronic myeloid leukemia (CML) patients. Early prediction of response to imatinib cannot be anticipated. We used a standardized quantitative reverse-transcriptase polymerase chain reaction (QRT-PCR) for BCR-ABL transcripts on 191 out of 200 late-chronic phase CML patients enrolled in a phase II clinical trial with imatinib 400 mg/day. Bone marrow samples were collected before treatment, after 12, 20 and at the end of study treatment (52 weeks) while peripheral blood samples were obtained after 2, 3, 6, 10, 14, 20 and 52 weeks of therapy. The amount of BCR-ABL transcript was expressed as the ratio of BCR-ABL to beta2-microglobulin (beta2M). We show that, following initiation of imatinib, the early BCR-ABL level trends in both bone marrow and peripheral blood samples made it possible to predict the subsequent cytogenetic outcome and response. We propose this method as the method of choice for monitoring patients on imatinib therapy. QRT-PCR studies may be able to identify degrees of molecular response that predict both complete cytogenetic response and long term stability, as well as patterns of response that provide an early indication of relapse and imatinib resistance.
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PMID:Prediction of response to imatinib by prospective quantitation of BCR-ABL transcript in late chronic phase chronic myeloid leukemia patients. 1640 13

A 14-year-old child presented with generalized lymphadenopathy and massive hepatosplenomegaly. Peripheral smear and bone marrow examination were suggestive of Ph' positive chronic myeloid leukemia (CML) in chronic phase. However, lymph node biopsy showed extramedullary blast crisis with evidence of myeloid and T cell markers in blasts. Reverse transcriptase-polymerase chain reaction from lymph node aspirate revealed transcript for bcr-abl p210. Thus, we present here a unique case of childhood CML with extramedullary biphenotypic blast crisis (myeloid/T cell type) at initial presentation with bone marrow remaining in chronic phase. This case provides further evidence to the highly heterogeneous presentation of CML.
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PMID:Biphenotypic extramedullary blast crisis as a presenting manifestation of Philadelphia chromosome-positive CML in a child. 1745 89

We report a case of chronic myelogenous leukemia displaying a variant Philadelphia translocation t(11;22)(q25;q11.2). Breakpoint 11q25 has not previously been reported. Reverse transcriptase polymerase chain reaction and fluorescence in-situ hybridization demonstrated the BCR/ABL rearrangement.
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PMID:[Chronic Myelogenous Leukemia with a Variant Philadelphia Translocation: t(11;22)(q25;q11.2).]. 1815 33

Nested reverse-transcriptase polymerase chain reaction (rt-PCR) was performed on 58 leukemia patients at BIRDEM Laboratory, as a pioneering work in Bangladesh. Thirty of themwere examined for the presence of BCR-ABL being clinically and morphologically diagnosed as chronic myeloid leukemia (CML) and 28 for PML-RARalpha fusion transcripts being clinically and morphologically diagnosed as acute promyelocytic leukemia (APL/ AML M3). The cases were selected for targeted therapy with imatinib mesylate and all-Trans retinoic acid (ATRA) to treat CML and APL respectively. Samples were received either before commencement or during therapy. In the positive cases, amplified DNA products were visible after gel electrophoresis and were reported accordingly. In case of BCR-ABL, positive results were found for five out of six (83.33%) untreated cases and 11 out of 24 (45.83%) treated cases. Positive results for PML-RARalpha were found for 12 out of 14 (85.70%) untreated cases and 11 out of 16 (68.75%) treated cases. A strong positive correlation was found between duration of treatment and negativity of PCR results in both the cases. In present times, the detection of minimal residual disease in patients undergoing treatment for hematological malignancies has become an important goal, not only to monitor the effectiveness of therapy but also to detect an impending relapse. This is the first time in Bangladesh that rt-PCR method is being employed to detect or monitor the presence of abnormal fusion genes in hematological malignancies.
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PMID:Rt-PCR method for diagnosis and follow-up of hematological malignancies: first approach in Bangladesh. 1878 70


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