UMLS:C0023473 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0023473 (chronic myeloid leukemia)
18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expansion of the Philadelphia (Ph) chromosome positive clone in chronic myeloid leukemia (CML) may depend on its capacity to suppress the proliferation of Ph-negative stem cells, but this proliferative advantage might, in certain circumstances, be reversible. Various lines of evidence suggest that Ph-negative cells, albeit in a suppressed state, must still be present. As recently suggested, the expansion of 'putative' normal Ph-negative hemopoietic stem cells might have, in certain circumstances, a proliferative advantage over the Ph clone in CML. This suggests that the treatment of CML with intensive chemotherapy might allow the collection of Ph-negative hemopoietic cells in the early phase of recovery. Eight patients with acute phase chronic myelogenous leukemia (AP-CML) were treated with idarubicin, intermediate dose cytarabine and etoposide. During recovery from bone marrow aplasia, when the white blood cell count reached 0.3-1 x 10(-9), blood cells were collected with 2-5 (median 3) consecutive leukapheresis. In 5/8 patients, these peripheral cells were Ph-negative at the cytogenetic analysis. Moreover, in one case the polymerase chain reaction analysis performed to detect the presence of minimal residual disease in the cells collected by leukapheresis was negative, further confirming that this approach may induce a very high degree of suppression of the Ph-positive clones. After complete recovery, these five patients were subsequently treated with high-dose etoposide, cyclophosphamide and total body radiation (10 Gy, single dose) followed by reinfusion of Ph-negative peripheral blood stem cells. All these patients received cyclosporine A post-autotransplant in an attempt to induce acute graft-versus-host-disease. Three of 5 patients remain in clinical and cytogenetic remission 5-15 months post-transplant. It is concluded that Ph-negative peripheral blood stem cells can be recovered from patients with AP-CML and used successfully to restore Ph-negative hemopoiesis after high dose therapy.
...
PMID:Therapy of acute phase chronic myelogenous leukemia with intensive chemotherapy, blood cell autotransplant and cyclosporine A. 167 80

Diagnosis of leukemia and lymphoma has been made by morphological, cytochemical, and immunophenotypical methods. Recently molecular biological approaches have been introduced to clarify the cellular lineage of the tumor cells and to demonstrate the monoclonality. Southern blot analysis using immunoglobulin (Ig) and T cell receptor (TcR) genes revealed the presence of monoclonal components in some cases of angioimmunoblastic lymphadenopathy (AILD), in which demonstration of monoclonality was difficult by conventional methods. In preB-ALL, many cases had rearranged IgH and TcR genes simultaneously. These "dual genotype" cases were found to be of accidental involvement of TcR gene in the process of making effective IgH gene rearrangements by the precise analysis of rearranged IgH gene structures. The rearranged TcR gene which was detected in initial lymphoblastic lymphoma cells, was observed in relapsed blasts after lineage conversion to myeloid leukemia, which indicates the same clonal origin. Diagnosis and detection of minimal residual disease by the polymerase chain reaction (PCR) are now recognized as sensitive methods. PCR using oligonucleotides common to each VH and JH gene detects the rearranged IgH gene sensitively. PCR using primers located on the translocation boundary, such as bcr and abl in CML, is very useful in the diagnosis and pursuit of the disease course. PCR study also can be applied to the detection of alteration of some particular genes such as tumor suppressor genes.
...
PMID:[Molecular diagnosis of leukemia and lymphoma]. 176 82

In vitro amplification of genomic or cDNA sequences by polymerase chain reaction (PCR) is one of the most powerful tools in recent molecular biology. More than 10(5) copies of DNA sequence ranging from 50 bp to 7 kb can be synthesized in a couple of hours. Ever since its development, PCR has attracted much attention because this strategy would allow the detection of minimal residual disease (MRD) at a very low level. The first successful application of this ultra-sensitive technique was the detection of residual tumor cells carrying a 14;18 translocation in follicular lymphoma. The abnormal transcripts caused by 9;22 translocation in chronic myelocytic leukemia (CML) was also exploited for the amplification to detect the MRD. These techniques have successfully shown the detection of one leukemic cell in 100,000 normal cells. Besides leukemic specific sequences caused by chromosome and gene translocations, unique sequences caused by rearrangements in IgH or TCR gamma, delta chain genes have been used as clonal markers for tumor cells. By targetting these sequences for PCR amplification, almost all ALL patients can be analyzed for MRD. The successive measurement of MRD might contribute to improvement of treatments for leukemic patients.
...
PMID:[The detection of minimal residual disease in leukemia by in vitro DNA amplification]. 177 67

In chronic myelogenous leukemia (CML), amplification of a segment of bcr-abl messenger RNA (mRNA) by polymerase chain reaction (PCR) can be used to detect minimal residual disease after bone marrow transplantation (BMT). Previous studies have shown that this sensitive technique can often detect small numbers of leukemia cells in patients who are otherwise in complete remission. Nevertheless, the clinical significance of PCR positivity remains unclear because the majority of patients with PCR-detectable bcr-abl mRNA can remain disease-free for prolonged periods after allogeneic BMT. In the present studies, we applied PCR to detect bcr-abl-positive cells in 100 serial blood or BM samples from 24 patients with CML who underwent CD6 T-cell-depleted allogeneic BMT. After BMT, bcr-abl mRNA could be detected in 20 patients (83.3%) during complete cytogenetic or clinical remission. Patients in whom PCR positivity was sustained over time had a higher probability of CML relapse than patients in whom PCR was intermittently negative (P = .0095, log rank test). PCR detection of bcr-abl transcript between 2 and 10 weeks post-BMT also was associated with a high probability of subsequent relapse (P = .023, log rank test). In eight selected patients, we used a titration assay of the PCR-amplified product to estimate the number of residual tumor cells in each clinical sample post-BMT. PCR results in four patients showed a continuing increase in the number of tumor cells from early posttransplant until either cytogenetic or clinical relapse could be detected by conventional methods 1 to 2 years later. In contrast, PCR detected either no leukemia cells or relatively low and stable numbers of residual tumor cells throughout the follow-up period in four patients who remained in clinical remission. These results show that detection of the bcr-abl transcript by PCR after allogeneic BMT in patients with CML has important prognostic value. Estimation of the number of tumor cells in serial analyses can also be used to detect proliferation of the residual leukemic population. Sensitive detection of minimal residual disease can be used to assess the effectiveness of the transplant preparative regimen and to direct and evaluate further therapy post-BMT, before the development of overt relapse.
...
PMID:Clinical significance of bcr-abl gene rearrangement detected by polymerase chain reaction after allogeneic bone marrow transplantation in chronic myelogenous leukemia. 182 68

Recent contributions from molecular biology, biotechnology and recombinant DNA applications have led to important clinical and therapeutic advances in chronic myelogenous leukemia (CML). Developments in the methodology of genetic investigation have clarified the molecular alterations brought about by the appearance of the Philadelphia chromosome. It is possible that the hybrid bcr/abl gene plays an important role in the pathogenesis of CML by subverting the mechanism of homeostasis through the uncoordinated activation of cell growth stimulating and regulating factors. Further improvements have been brought about by the polymerase chain reaction (PCR) which permits an indirect identification of the fusion gene and the study of minimal residual disease during remission after chemotherapy and bone marrow transplantation (BMT). Clinical trials have shown that alpha-interferon, alone or in association with chemotherapy, induces long term clinical and cytogenetic remission in those CML patients in whom BMT from either related or unrelated donors cannot be performed. Allogeneic BMT seems to be the treatment of choice in younger people. However, since a minority of subjects have HLA identical siblings, the possibility of using unrelated donors to provide long term disease free survival has been explored even if the availability of a compatible donor is the primary limiting factor. The development of in vivo and in vitro purging procedures has aroused new interest in autologous bone marrow transplantation. This procedure benefits particularly from biotherapeutic agents which selectively act on the marrow by suppressing bcr/abl positive cells.
...
PMID:Chronic myelogenous leukemia: state of the art. 184 Aug 16

The Polymerase Chain Reaction (PCR) was used to evaluate minimal residual disease in 21 Ph+ CML patients at various intervals after allogeneic bone-marrow transplantation (ABMT) by amplification of bcr-abl cDNA. All patients were cytogenetically Ph- at the moment of molecular analysis. Of these 76% were PCR negative, 24% positive for bcr-abl transcripts. 100% of the Cyclosporine A/Methotrexate treated patients (7/7) were negative. Severe chronic GvHD was twice as frequent in PCR positive patients (60%) than in negative ones (31%). The only patient who relapsed during follow up was PCR positive. The two longest survivors were PCR negative. These data are still insufficient for assessing the predictive value of PCR analysis in CML. Patients. 25 patients with Ph+ CML at diagnosis were enrolled in this study. Two died soon after BMT because of infection for failure of engraftment/early relapse, two were Ph chromosome positive and PCR+, and were therefore dismissed from this study. All remaining 21 patients were cytogenetically Ph- at the time of molecular analysis and underwent ABMT from matched donors. All patients were conditioned with cyclophosphamide and TBI: 330 cGy the three days prior to transplantation (990 cGy total, treatment B), or 200 cGy two times daily for three days (1200 cGy total, treatment A). In 3 cases the marrow was treated for GvHD prophilaxis with Campath alone or Campath plus BT 5/9 monoclonal antibodies (1). All patients were treated with Cyclosporin A (CS) 5 mg/kg i.v. from the day prior to transplantation until 25-30 days after; 9 of these were treated with CS plus Methotrexate (MTX).
...
PMID:An assessment of chimeric transcript detection in CML patients after bone marrow transplantation. 187 98

Current induction therapies for acute and chronic leukemias and the lymphomas have achieved significant complete remission rates. Despite this initial success, disease recurrence remains a major problem. Relapse from clinically undetectable residual malignant cells is the most likely mechanism of recurrence. Of crucial importance to the clinician is the accurate detection of residual malignant cells prior to clinical relapse. Standard approaches to evaluate for this minimal residual disease (MRD) allow detection only when the malignant clone exceeds 1%. Patients in remission, however, may frequently have residual neoplastic cells that are far below this level. Recently, several investigators have adapted the polymerase chain reaction (PCR) to detect tumor-specific DNA or RNA sequences. This approach is highly sensitive (able to detect 1 malignant cell in 10(6) normal cells). The application of this technique to the study of MRD thus far has been limited to tumors in which specific DNA or RNA sequence data are available. This review describes the application of PCR to the detection of MRD in patients with chronic myelogenous leukemia, acute lymphoblastic leukemia, and follicular small cleaved cell lymphoma. Because the number of clinical studies and length of follow-up is limited, detection of MRD by PCR is at present largely a research tool and the biological significance of MRD as determined by PCR must await further studies.
...
PMID:Application of the polymerase chain reaction for detection of minimal residual disease of hematologic malignancies. 189 4

The first consistent karyotypic abnormality found to be associated with neoplastic disease was the Philadelphia (Ph) chromosome (Nowell & Hungerford, 1960). Furthermore, the best-studied example of translocation-mediated gene activation occurs in leukaemia patients bearing this abnormality (reviewed by Kurzrock et al, 1988). In these individuals, the Ph translocation (t(9;22)(q34;q11)) results in transposition of the ABL proto-oncogene from chromosome 9q34 to 22q11, where it is fused with part of the BCR gene. It is now known that as a result of the Ph translocation, p160BCR and p145ABL (the normal BCR and ABL gene products) are replaced by p210BCR-ABL. This aberrant protein constitutes the molecular fingerprint of CML. The enhanced tyrosine phosphokinase enzymatic activity (a property possessed by some growth factor receptors and transformation-inducing oncogenes) of p210BCR-ABL implicates a direct role for this molecule in the pathogenesis of CML. Because the Ph translocation is present in the early chronic phase, the union of the BCR and ABL genes is probably involved in the initiation of the leukaemic process. The secondary molecular forces driving progression of CML to blast crisis are however unknown, and may differ from patient to patient. Approximately 10% of CML patients lack a Ph chromosome. One-half of these individuals have bcr rearrangement and express p210BCR-ABL. Ph+ and Ph- bcr+ (p210+) CML are identical and should be treated the same. Molecular follow-up of diploid bcr+ CML patients is essential for detection of persistent malignancy after therapy. The presence of a specific marker--the BCR-ABL message--permits the development of new diagnostic approaches for CML. For instance, detection of a BCR-ABL message with the use of the highly sensitive polymerase chain reaction, a technique capable of detecting up to one leukaemia cell amongst one million normal cells, yields important information about minimal residual disease. Finally, the use of therapy directed against the BCR-ABL product may be a worthwhile strategy which deserves investigation, and may prompt a new era of tumour-specific treatment.
...
PMID:The molecular pathology of chronic myelogenous leukaemia. 193 6

Autologous bone marrow transplantation (ABMT) has developed considerably in the past 15 years and is now a routine procedure for the consolidation of acute leukemias, non-Hodgkin's lymphomas and Hodgkin's disease. In addition, ABMT has been tested in multiple myeloma (MM) and even considered in highly selected cases of chronic myelocytic leukemia (CML). Interest has resulted from the discovery of new purging procedures such as long-term cultures with or without serum-free media containing various lymphokines, the evaluation of cryoinjury on malignant cells, the increased detection of minimal residual disease using PCR, and the acceleration of hemopoietic recovery post-ABMT through the use of peripheral blood stem cells and/or lymphokines. Results presented include data from the international (ABMTR) and European (EBMT) registries, and our own unit in Paris. With respect to acute leukemias, (a) the EBMT listed 1,688 patients. The overall results were as follows: for patients autografted in complete remission (CR) 1, the leukemia-free survival and relapse rate at 7 years were 48 +/- 2% and 41 +/- 3% for AML and 44 +/- 5% and 45 +/- 5% in acute lymphoblastic leukemia (ALL), respectively. In CR2, the figures were 34 +/- 4% and 54 +/- 5% for AML and 32 +/- 3% and 62 +/- 4% for ALL, respectively. Patients not relapsing at 1 year post-ABMT had a probability of being cured at 7 years of 86 and 71% if autografted in CR1 and CR2 for AML and 81 and 59% for ALL, respectively. Multivariate analysis of relapse rates in several subpopulations confirmed the efficacy of marrow purging in AML CR1: in patients transplanted prior to January 1988 (minimum follow-up of 2 years), the relapse rate with purged marrow was 35 +/- 5% vs. 47 +/- 3% (p less than 0.005). (b) In Paris, St-Antoine, using TBI and marrow purged with mafosfamide at levels individually adjusted (Blood 1986;67:1367), the probability of remission and DFS were 84 and 62% in AML CR1 63 and 59% in ALL CR1, respectively. There was a statistically significant relationship between the relapse rate and the residual amount of CFUGM progenitors in the marrow after purging. The cutoff point was 0.3%, with a relapse rate of 54% in those receiving marrow containing the higher residual CFUGM fractions and only 29% in those receiving less. With respect to non-Hodgkin's lymphomas, the EBMT listed 698 patients. In intermediate or high grade lymphomas, the DFS at 6 years was 30% and 18% in sensitive and resistant relapses, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Autologous bone marrow transplantation in hematological malignancies. 204 65

N-ras oncogenes activated by point mutation have been frequently detected in various types of human leukemias. Analysis of a large number of leukemias revealed that activated N-ras oncogenes were observed preferentially in AML, AMoL, T-ALL and Null-ALL but rarely in CML and B-cell leukemia. These results suggest that N-ras oncogene plays an important role in human leukemogenesis. Activated N-ras oncogenes were also detected in myelodysplastic syndrome (MDS) that is considered to be a preleukemic disease. MDS patients bearing an activated N-ras oncogene frequently showed leukemic progression of the disease, suggesting that an activated N-ras oncogene can be a critical factor for prognosis of MDS patients. Thus, detection of an activated N-ras oncogene is useful for diagnosis, prognostic evaluation and therapeutic decision. Recently, we demonstrated that detection of the minimal residual disease by analysis of N-ras oncogene can lead to improvement of the remission rate in leukemias. Moreover, we made it possible to screen N-ras oncogene by a sensitive non-radioactive method. Our research procedure seems to be a good model for clinical application of the molecular biological technique.
...
PMID:[Activation of ras oncogene in myelodysplastic syndrome and acute myelogenous leukemia]. 205 67

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>