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)

Hybrid fusion genes are specific tumor markers of several leukemic subtypes. The use of reverse transcription-polymerase chain reaction (RT-PCR) to amplify chimeric cDNAs allows sensitive detection of the neoplastic clone for diagnostic and monitoring studies in these leukemias. Nonetheless, the clinical relevance of minimal residual disease (MRD) evaluation by PCR remains controversial. In this study, 9 patients (pts) with acute promyelocytic leukemia (APL) in long-term remission for 4 to 12 years were analyzed for the presence of MRD by RT-PCR amplification of the specific PML/RAR-alpha fusion gene. Seven pts had been treated with conventional chemotherapy (CHT) alone, 1 had undergone allogeneic bone marrow transplantation (BMT), and 1 autologous BMT as consolidation therapy after CHT. In 8 cases, the presence of the t(15;17) rearrangement could be documented in diagnostic BM specimens by cytogenetic and/or molecular analysis. A two-rounds "nested" RT-PCR assay with sensitivity levels of 1 in 10(5) was used to analyze BM samples collected at 32 to 141 months from the achievement of complete remission (CR). In no cases were residual PML/RAR-alpha transcripts detectable in these remission controls. All patients are in unmaintained CR at 48 to 154 months from CR and at 6 to 17 months from PCR evaluation. These results suggest that long-term survival of APL is associated with eradication of cells carrying the specific PML/RAR-alpha rearrangement, indicating that PCR negativity should be considered the therapeutic goal in these patients. Our findings further strengthen the clinical relevance of PCR monitoring studies in APL, as opposite to other leukemic subtypes (chronic myeloid leukemia and acute myeloid leukemia-M2) in which the prognostic significance of PCR evaluation is unclear.
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PMID:Absence of reverse transcription-polymerase chain reaction detectable residual disease in patients with acute promyelocytic leukemia in long-term remission. 826 Jun 93

New developments in relation to chronic myelogenous leukemia (CML) are characterized by progress in knowledge of pathogenesis, diagnostic improvement such as nosology of Philadelphia-negative CML and diagnosis of minimal residual disease by molecular techniques, advances in drug therapy with hydroxyurea or interferon alpha, and progress in bone marrow transplantation through availability of unrelated donors. In addition, the recognition of suitable prognostic parameters indicates that risk adapted therapy may become possible.
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PMID:[Chronic myeloid leukemia. State of the art, May 1993]. 829 89

Current progressive chemotherapy and transplantation induce not only remission but complete cure. By this reason, the detecting system for MRD must be established in complete remission phase. In this study, we showed the detecting for MRD by molecular biology techniques in the patients with non-Hodgkin's lymphoma, CML, B-ALL and AML. 1) Malignant cells could be detected in peripheral blood or bone marrow cells by Southern blot analysis in 15 of 30 patients with non-Hodgkin's lymphoma. 2) In CML patients, BCR/ABL fusion gene was positive by RT-PCR for 6 months after BMT, 4 patients became undetectable for 7 months after BMT. 3) Rearrangement of Ig H has been disappeared in 12 months after achieved complete remission the patients with B-ALL. In conclusion, the detection for MRD remain an important goal for therapy including chemotherapy and bone marrow transplantation in hematopoetic malignancy.
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PMID:[Detection of residual malignant cells in patients with hematopoietic malignancy]. 831 24

Acute lymphoblastic leukemia (ALL) is thought to arise from the clonal expansion of a single transformed precursor cell. However, an oligoclonal Ig heavy chain (IgH) rearrangement pattern has been observed in 30% of ALL patients and was shown to be the result of ongoing rearrangement events. The extent and nature of these ongoing rearrangement processes in individual patients has so far remained obscure. We performed a detailed analysis of leukemic VHDJH rearrangements in three children with B-precursor ALL at diagnosis and one B-lymphoid blast crisis of a child with Ph+ chronic myeloid leukemia at diagnosis and relapse. The children were selected because they presented with multiple IgH rearrangements on Southern blot analysis. Polymerase chain reaction analysis of leukemic cells from two B-precursor ALL patients showed exclusively two groups of related sequences resulting from VH gene replacement events. Most VH gene replacements involved 3' located acceptor VH genes. Analysis of cells from the other B-precursor ALL patient showed exclusively related sequences as a result of VH gene joinings to a pre-existing DJH rearrangement. In the B-lymphoid blast crisis, a single germline precursor cell had generated multiple unrelated rearrangements and additional groups of related rearrangements resulting from VH to DJH joinings. Direct proof for the VH to DJH joining mechanism was obtained by amplification of the expected preexisting DJH rearrangements. Our findings suggest that the pattern of ongoing rearrangements in an individual patient reflects the IgH rearrangement status of the precursor cell at the time of malignant transformation. Sequence analysis of VHDJH rearrangements at diagnosis may therefore allow a prediction of the reliability of complementarity determining region 3 probes for the detection of minimal residual disease.
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PMID:Distinct ongoing Ig heavy chain rearrangement processes in childhood B-precursor acute lymphoblastic leukemia. 832 13

We diagnosed a patient with chronic myelogenous leukemia (CML) in chronic phase (CP) on the basis of clinical findings, Ph1 chromosome detected by cytogenetic analysis, and bcr-abl fusion mRNA detected by reverse transcriptase-dependent polymerase chain reaction (RT-PCR). One month after diagnosis, the patient developed extramedullary blast crisis in the lymph nodes, and then medullary blast crisis in the bone marrow, in which different surface markers were shown. Combination chemotherapy with BH-AC, VP16, and mitoxantrone was administered; this resulted in rapid disappearance of the lymphadenopathy, restoration of normal hematopoiesis, and no Ph1 chromosome being detected by cytogenetic analysis. RT-PCR performed to detect the residual Ph1 clone revealed that although the Ph1 clone was preferentially suppressed, it was still residual. The intensive chemotherapy regimen preferentially suppressed the Ph1-positive clone and led to both clinical and cytogenetic remission in this patient with BC of CML; we suggest that RT-PCR is a sensitive and useful method for detecting minimal residual disease during the clinical course of this disease.
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PMID:Disappearance of Ph1 chromosome with intensive chemotherapy and detection of minimal residual disease by polymerase chain reaction in a patient with blast crisis of chronic myelogenous leukemia. 836 86

We have developed a competitive polymerase chain reaction (PCR) titration assay that estimates the number of BCR-ABL transcripts in chronic myeloid leukemia patients to monitor minimal residual disease after bone marrow transplantation (BMT). The assay gave reproducible results and allowed differences in BCR-ABL message levels of half an order of magnitude to be distinguished. Of 91 patients studied by nonquantitative PCR, 28 who had a positive PCR result on at least one occasion posttransplant were analyzed by competitive PCR. Seventeen patients had no evidence in their marrow of cytogenetic relapse during the period of observation; BCR-ABL transcript numbers in these cases ranged from approximately 10 to 800/micrograms RNA. Ten of the 11 patients who relapsed cytogenetically were studied when Philadelphia-positive metaphases were first detected in their marrow; transcript numbers ranged from 1,600 to 7 x 10(5)/micrograms RNA. Patients in hematologic relapse had between 9 x 10(4) and 10(6) BCR-ABL transcripts/micrograms RNA. Patients who progressed from cytogenetic remission to cytogenetic relapse and then to hematologic relapse had increasing numbers of BCR-ABL transcripts in their blood. Three patients had clear evidence of rising numbers of BCR-ABL transcripts before routine detection of cytogenetic relapse. Conversely patients without cytogenetic relapse generally had low or falling numbers of transcripts. We conclude that serial monitoring of residual disease post-BMT by estimating the number of BCR-ABL transcripts provides more information than conventional cytogenetics or nonquantitative PCR and may identify patients in need of therapeutic intervention before the onset of overt relapse.
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PMID:Competitive polymerase chain reaction to estimate the number of BCR-ABL transcripts in chronic myeloid leukemia patients after bone marrow transplantation. 840 Feb 43

Interferon-alpha produces a complete hematologic and cytogenetic remission in approximately 20% of patients with chronic myelogenous leukemia (CML). In this study, we applied fluorescent in situ hybridization (FISH) methodology to examine the possibility that a low level of proliferating Philadelphia-chromosome-positive (Ph+) cells may be present in interferon-treated CML patients who have achieved complete cytogenetic remission (as defined by the absence of Ph chromosome in 20-25 metaphases analyzed). Ten such patients in remission for 6-35 months were studied by this technique, in which a chromosome-22-specific DNA painting probe was used to detect leukemic cells with the characteristic 9;22 chromosomal translocation. In six of the 10 patients (60%), 3-9% Ph+ metaphases were detected. No Ph+ cells were observed in nine control individuals. Thus, this study demonstrates that FISH technology is more sensitive than conventional cytogenetic analysis for the detection of minimal residual disease in CML.
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PMID:Detection of residual proliferating leukemic cells by fluorescence in situ hybridization in CML patients in complete remission after interferon treatment. 842 70

Recent advances in molecular cytogenetics of leukemia is reported with special reference to the pathogenesis, diagnosis, prognosis, and potential gene therapy. Regarding leukemogenesis, we found that neocarzinostatin induced a variety of deletions and reciprocal translocations. Among these random chromosome abnormalities, two reciprocal translocations which were specific for certain leukemias could be observed; t(11;14)(q13;q32) and t(7;11)(p15p13). This fact suggests that a translocation carrying oncogene rearrangement may be of potential relevance to the leukemogenesis. The success in making a subgroup (FAB classification) identified a number of subtype-specific translocations in leukemias. It has been suggested that an initiation or progression-associated event is mediated through a gross chromosomal change. The molecular characterization of chromosomal rearrangement leads to the identification of genes involved in leukemia. Our recent works in molecular cytogenetics of chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), FAB-M3 and -M4 were shown in this article. Since rearrangement of relevant genes were cloned, PCR made it feasible to detect minimal residual disease at 10(-6) level after intensive treatment or bone marrow transplantation for CML, Ph-positive ALL, M3 and approximately half of childhood leukemia. Recently developed fluorescent in situ hybridization (FISH) using specific probes can visualize certain chromosomes or chromosomal segments. Ph translocation, for instance, is now demonstrated as three spot-signals in interphase nuclei using YAC (yeast artificial chromosome)-BCR clone. Lastly, the use of antisense oligonucleotides for the BCR-ABL junctions should result in the inhibition of growth of CML clone. The strategy using antisense molecules may be very powerful tool in the gene-targeting therapy for human neoplasms.
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PMID:[Recent advances in molecular cytogenetics of leukemia]. 847 75

The polymerase chain reaction (PCR) was used to amplify the bcr/abl transcript as a marker of minimal residual disease (MRD) in 76 patients with chronic myeloid leukemia (CML) subjected to allogeneic BMT and in complete hematological remission. We examined 56 patients transplanted in chronic phase (CP) and 20 in advanced phase (AD), including 16 in accelerated phase and four in blastic transformation. A total of 135 samples collected between 4 and 105 months from BMT were analyzed and the PCR analysis was positive in 33 (24%) samples from 20 patients. The bcr/abl chimeric transcript was detected in 7/13 (54%) patients analyzed within 1 year and in 21/88 (23%) beyond 1 year from BMT. Fluctuation of the residual disease at the molecular level in individual patients was recorded. The results have been correlated with a number of clinical parameters obtained before and after BMT; among the tested variables only the phase of the disease at BMT was associated with higher frequency of PCR positivity after BMT. The probability of finding persisting disease 1 year beyond BMT was significantly higher (P = 0.00005) in patients allografted in AD (14/26, 54%) as compared to patients grafted in CP (7/62, 11%). At any interval from BMT the difference between the two groups remained statistically significant: the bcr/abl transcript was present in 5/31 patients transplanted in CP compared to 9/15 patients transplanted in AD (P = 0.003) between 12 and 36 months from BMT, and in 2/31 CP vs 5/11 AD patients (P = 0.008) beyond 36 months from BMT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:bcr/abl chimeric transcript in patients in remission after marrow transplantation for chronic myeloid leukemia: higher frequency of detection and slower clearance in patients grafted in advanced disease as compared to patients grafted in chronic phase. 852 78

Allogeneic bone marrow transplantation (BMT) is the treatment of choice for hematologic malignancies resistant to conventional chemotherapy and for patients who are at high risk for relapse. Until recently, no cure could be offered to patients relapsing following allogeneic BMT. We present our long-term observations of the first patient with remission reinduced by allogeneic cell therapy (allo-CT) using donor peripheral blood lymphocytes (PBL). In addition, we review the cumulative international experience with allo-CT used to treat 163 patients, 105 with CML and 58 with other hematologic diseases, who relapsed following allogeneic BMT. The first patient treated by allo-CT was diagnosed with acute resistant pre-B lymphoblastic leukemia (ALL) in extensive third hematologic and extramedullary relapse shortly after BMT. He was given infusions of donor (sister) PBL in multiple increments. Subsequently, he developed mild, reversible graft-vs-host disease (GVHD) in parallel with regression of all hematologic and cytogenetic disease manifestations. More than 8 years after allo-CT, he is disease-free with Karnofsky score 100% and no evidence of residual male cells by PCR. International data show that relapse after BMT was successfully reversed by donor PBL treatment in 97 of 158 evaluable patients; 72/100 (72%) with chronic myeloid leukemia (CML) and 25/58 (44.8%) with other malignant hematologic diseases including acute leukemia, lymphoma, and myelodysplastic syndrome. T cell depletion (TCD) for prevention of GVHD was performed for 60/105 (57%) patients with CML and 31/58 (53.4%) patients with other hematologic malignancies. Complete response after allo-CT was obtained in recipients of both TCD-BMT and unmodified BMT. GVHD due to allo-CT developed in 86/158 (54.4%) of the patients, 63/100 (63.0%) with CML and 23/58 (39.6%) with other hematologic diseases. alpha-interferon (IFN-alpha) was given to 67.9% of patients with CML and 28.1% of patients with other diseases. The cumulative experience shows that allo-CT can successfully reverse chemoradiotherapy-resistant relapse of acute leukemia and even more effectively of chronic leukemia independently of alpha-interferon therapy. Although GVHD was frequent among responders, accompanied occasionally by transient or irreversible marrow aplasia, remissions were also obtained in patients with no GVHD. Allo-CT should therefore be considered as treatment of choice for overt relapse or de novo minimal residual disease post-BMT. Administration of donor peripheral blood lymphocytes in graded increments at an early stage of relapse may be the best approach for combining optimal timing at the stage of minimal disease while controlling and minimizing the risk of GVHD on an individual basis.
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PMID:Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes. 854 46


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