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)

Double fluorescence in situ hybridization was used to detect Philadelphia (Ph) chromosomes in interphase nuclei and metaphases of patients with chronic myeloid leukemia. Application of cosmid probes for 3' ABL and 5' BCR sequences gave better results than libraries for chromosomes 9 and 22. The present approach may provide an alternative method for monitoring minimal residual disease in Ph+ CML patients.
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PMID:Detection of the Philadelphia chromosome in interphase nuclei. 226 53

The Ph1 chromosome has two molecular subtypes: a bcr-positive seen in CML and some cases of ALL, and the bcr-negative subtype mainly seen in ALL. In CML, because of the restriction of chromosome 22 breakpoints to the bcr, Southern analysis to detect bcr rearrangements also can be used to detect the Ph1 chromosome. In contrast, the translocation breakpoints on the Ph1 chromosome are scattered in ALL, so that other methods such as PFGE and PCR are necessary to detect the Ph1 chromosome. In both CML and ALL, use of these methods to detect molecular abnormalities may be superior to cytogenetics in detecting chromosomal abnormalities. Southern analysis also can be used in CML to map breakpoint locations within the bcr. This may offer prognostic information as to the length of chronic phase, but there is conflicting information as to the validity of this approach. The modified PCR (using cDNA from mRNA) can be used to detect the Ph1 chromosome and to define which of the molecular subtypes are present. The exquisite sensitivity of this method, which is capable of detecting as little as a single abnormal molecule of RNA or DNA, makes it suited for the detection of minimal residual disease in both CML and ALL. This is particularly useful after intensive therapies, such as bone marrow transplantation. Whether these low levels of fusion gene expression are of prognostic significance is still unclear.
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PMID:Molecular methods to detect the Philadelphia chromosome. 227 77

The success of autologous bone marrow transplantation (ABMT) in acute leukemia (AL) in complete remission (CR) is limited by the high relapse rate. It is generally accepted that minimal residual disease (MRD) plays a major role in determining the relapse of disease. In our study we investigated in adult acute leukemia and in chronic myelogenous leukemia (CML), the efficacy of ex vivo marrow purging with mafosfamide (an in vitro derivative of cyclophosphamide). We also describe an improved purging approach ("programmed method") based on the evaluation of sensitivity to the drug measured in each individual patient prior to ABMT. The analysis of clinical data in terms of disease-free survival (DFS) shows that the "programmed method" gives significantly better results than those obtained using the standard dose of mafosfamide (80% DFS in 18 AL patients vs. 44% in 33 ANLL patients and 33% in 56 ALL patients). The evaluation of the CR to purging interval in ALL and ANLL shows that a period of greater than 6 months is necessary to obtain longer DFS. Considering pre-transplant regimens, busulfan-cyclophosphamide is more effective in ANLL, and cyclophosphamide-fractionated total body irradiation is the best treatment for ALL. The studies using mafosfamide marrow purging in CML demonstrate that the drug is able to achieve a decrease of the Ph1+ marker. Three patients who showed conversion of this cytogenetic marker have been autografted with interesting clinical results.
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PMID:Pharmacological-mediated purging with mafosfamide in acute and chronic myeloid leukemias. The Italian Study Group. 230 82

Twenty-six patients with acute leukaemia and 14 with high-grade lymphoma received cytosine arabinoside (ara-C) at a twice daily dose of 2 g/m2 administered as a 3-h infusion. Thirty-four patients received 12 doses and six electively received four doses only. Complete remission was achieved in six of seven patients with acute myelogenous leukaemia (AML), one of two evaluable patients with blast crisis of chronic myeloid leukaemia and three of eight patients with acute lymphoblastic leukaemia (ALL). Three further patients with ALL had only minimal bone marrow infiltration after one cycle, toxicity precluding administration of a second. Three patients with AML who received four doses only showed no evidence of response. Four of 14 patients with lymphoma who received 12 doses, entered complete remission. Five additional patients died with minimal residual disease whilst severely neutropenic. A complete and a partial response were seen in two patients with immunoblastic and centrocytic lymphoma respectively who received four doses. These results confirm the activity of high-dose ara-C in patients with AML and suggest that it may also be a potentially useful agent in ALL and high-grade lymphoma, especially as the incidence of CNS toxicity is lower than that reported at higher doses.
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PMID:High-dose cytosine arabinoside: response to therapy in acute leukaemia and non-Hodgkin's lymphoma. 669 29

M195, a mouse monoclonal antibody reactive with the early myeloid antigen CD33, has been shown to target leukemia cells in patients and to reduce large leukemic burdens when labeled with 131I. A complementarity-determining region-grafted, humanized version (HuM195) has demonstrated similar targeting of leukemia cells without immunogenicity. We have studied two applications of therapy with 131I-M195. First, to intensify therapy prior to bone marrow transplantation (BMT), we combined 131I-M195 with busulfan and cyclophosphamide. Fifteen patients received first BMT for relapsed or refractory acute myelogenous leukemia or accelerated or blastic chronic myelogenous leukemia; four received second BMT for relapsed chronic or accelerated chronic myelogenous leukemia. Doses of 131I-M195 ranged from 120 to 230 mCi/m2. Few toxicities could be attributed to 131I-M195 therapy, and all patients engrafted. Eighteen patients achieved complete remission. Among those patients receiving first BMT, three have remained in unmaintained remission for 18+ to 29+ months. Six patients relapsed, including one with isolated central nervous system disease 32 months after BMT. Ten patients died in complete remission of transplant-related complications. Second, we studied whether 131I-M195 could reduce minimal residual disease and prolong remission and survival durations safely in patients with relapsed acute promyelocytic leukemia after they attained remission with all-trans-retinoic acid. Seven patients were treated with either 50 or 70 mCi/m2 131I-M195. Toxicity was limited to myelosuppression. As a measure of minimal residual disease, we monitored PML/RAR-alpha mRNA by reverse transcription PCR. Six patients had positive reverse transcription PCR assays prior to receiving 131I-M195; two converted transiently to negative. Median disease-free survival and overall survival of the seven patients were 8 (range, 3-14.5) months and 28 (range, 5.5-43+) months, respectively. This regimen compares favorably with others for relapsed acute promyelocytic leukemia. In an effort to avoid nonspecific cytotoxicity associated with 131I in future trials for minimal residual disease, we have conjugated short-range, alpha particle-emitting radioisotopes to HuM195 using a bifunctional chelate, 2-(p-isothiocyanatobenzyl)-cyclohexyldiethyl-enetriaminep entaacetic acid, with high efficiency and specific activities. 212Bi-HuM195 has demonstrated dose- and specific activity-dependent killing of HL60 cells in vitro. Injection of 213Bi-HuM195 into healthy BALB/c mice produced no effects on weight or viability.
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PMID:Radiolabeled anti-CD33 monoclonal antibody M195 for myeloid leukemias. 749 68

Recent progress in the development of diagnostic techniques has greatly facilitated the monitoring of minimal residual disease (MRD) in patients with hematologic neoplasia. The presence of genetic markers, such as the BCR/ABL rearrangement in chronic myelogenous leukemia (CML), has allowed highly sensitive detection of residual leukemic cells by polymerase chain reaction (PCR). However, complete eradication of the leukemic clone may not be a necessary prerequisite for long-term remission or cure. This observation limits the value of qualitative PCR analysis for prediction of progressive disease and highlights the need to monitor the proliferative activity of the malignant clone in order to permit timely detection of impending relapse. We have developed a quantitative PCR protocol based on the principle of competitive enzymatic amplification and demonstrated its applicability to the monitoring of treatment efficacy and early assessment of clonal expansion in patients with CML. We have introduced the term 'PCR relapse' for the detection of a proliferating leukemic clone by serial quantitative PCR (Q-PCR) analyses. At a recent meeting of the group of European Investigators on Chronic Myelogenous Leukemia (EICML Group) the use of Q-PCR investigation has been recommended for the monitoring of MRD, and the detection of PCR relapse was accepted as a basis for therapeutic decisions. This article discusses problems in the interpretation of MRD by PCR and presents guidelines for the clinical use of qualitative and quantitative PCR analyses.
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PMID:Clinical implications of qualitative and quantitative polymerase chain reaction analysis in the monitoring of patients with chronic myelogenous leukemia. The European Investigators on Chronic Myeloid Leukemia Group. 753 63

We compared two non-radioactive PCR methods, a single step PCR and a nested PCR, for detecting bcr-abl transcripts in patients with chronic myelogenous leukemia (CML). The nested PCR assay was about thousand times more sensitive than the single step PCR. In 75 clinical samples tested in parallel, the sensitivity for the single step PCR and the nested PCR was 43.2% and 91.9%, respectively. In all 17 samples of 9 patients before bone marrow transplantation (BMT), bcr-abl transcripts were detected by the single step PCR. After BMT, 5 (9.8%) of 51 samples of 4 patients were positive by the single step PCR and 17 (33.3%) of 7 patients by the nested PCR. These data indicate that single step PCR may miss minimal residual disease whereas nested PCR is a sensitive alternative to the use of radioactive probes.
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PMID:[Detection of bcr-abl transcripts in "minimal residual disease" in chronic myelogenous leukemia by nested polymerase chain reaction (PCR)]. 753 4

A monoclonal antibody which primarily reacted with Philadelphia chromosome (Ph1)-positive ALL cells was produced. The reactivity of a monoclonal antibody, KOR-SA3544 (IgG2a) was evaluated on normal hemopoietic cells, 68 leukemic cell lines and freshly obtained cells from 190 patients with leukemia and lymphoma. In cultured cells, KOR-SA3544 reacted with Ph1-positive ALL cell lines (5/5) and leukemic cell lines with 11q23 translocation (3/11). In lymphoid cells, KOR-SA3544 was reactive with all of Ph1-positive ALL (26/26), a part of common ALL (5/38) and one case of early B precursor leukemia with 11q23 translocation, but not with peripheral lymphocytes. Normal mature granulocytes were also strongly stained. In myeloid leukemias, KOR-SA3544 was positive (16/56) only in patients with acute myeloid leukemia with FAB-M2 and overt leukemia following myelodysplastic syndrome, but neither with other types of myeloid leukemias nor with blast crisis in chronic myelogenous leukemia. KOR-SA3544 recognized a 90 KDa protein on the membrane of a leukemic cell line, KOPN-57bi. In normal bone marrow, CD19+/KOR-SA3544+ cells were not identified, while Ph1-positive ALL cells were strongly positive for both antibodies. KOR-SA3544 is useful not only for making the diagnosis of Ph1-positive ALL but for detection of the minimal residual disease during remission.
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PMID:A novel monoclonal antibody, KOR-SA3544 which reacts to Philadelphia chromosome-positive acute lymphoblastic leukemia cells with high sensitivity. 754 76

The early detection of clonogenic cells able to survive cytotoxic therapy and to initiate a neoplastic process, defined as Minimal Residual Disease (MRD), represents a major objective for the development of new and more sensitive diagnostic methods. The cloning of different chromosomal translocations along with the application of the Polymerase Chain Reaction (PCR) technique has allowed the characterization of various hematological disorders at the molecular level. This approach has led to the development of PCR based assays able to detect a minimum number of malignant cells with very high specificity. In the present paper we discuss the use of PCR and its value as a predictor for relapse in lymphomas, chronic myelogenous leukemia and acute promyelocytic leukemia, characterized by the t(14;18) t(9;22) and t(15;17) translocations, respectively.
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PMID:[Use of polymerase chain reaction (PCR) in oncohematology. Detection of minimal residual disease]. 756 55

Fourteen patients treated by allogeneic bone marrow transplantation for chronic myelogenous leukemia (CML) were evaluated by the polymerase chain reaction (PCR) for bcr-abl-specific transcripts. Nine patients were transplanted in the first chronic phase, three in the second chronic phase, and two in the accelerated phase. All patients achieved a complete cytogenetic and hematologic remission after bone marrow transplantation. Twelve patients are alive (median, 18 months; range, 5-54 months) and two patients died early. bcr-abl mRNA was persistently detectable for 6 to 54 months in four patients (patients 1, 3, 4, 6). From two of them, DNA fingerprint analysis showed only donor type DNA although bcr-abl mRNA was detectable. bcr-abl mRNA was never detectable posttransplant in three patients (patients 2, 5, 13). Six patients had detectable bcr-abl mRNA (patients 8-12, 14): by 6 months, all of these patients were bcr-abl mRNA negative. One patient (patient 7) had detectable full bcr-abl mRNA again at 12 months, but was then negative at 20 months. Ten patients (patients 2, 4-8, 10-13) had never detectable Philadelphia (Ph1) chromosome t(9.22) translocation, whereas four patients had detectable Ph1 (patient 1, 3, 9, 14); by 6 months, three of four cases were negative. One patient (patient 1) had detectable Ph1 at 44 months, but was negative at 50 months. Three of six patients who initially had bcr-abl mRNA detectable posttransplant (patient 7-9) became negative for bcr-abl mRNA at the time of development of chronic graft-versus-host disease (GVHD). These results suggest that the detection of subclinical Ph1 positive cells by PCR is not associated with imminent clinical or cytogenetic relapse. Moreover, graft-versus-leukemia (GVL) activity may contribute to the treatment of minimal residual disease in CML after allogeneic bone marrow transplantation.
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PMID:Predicting relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation by bcr-abl mRNA and DNA fingerprinting. 757 10


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