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)

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.
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PMID:Clinical significance of bcr-abl gene rearrangement detected by polymerase chain reaction after allogeneic bone marrow transplantation in chronic myelogenous leukemia. 182 68

A highly sensitive enzyme-linked immunoassay (ELISA) was developed to detect and quantify the tumor marker, 1-methylinosine (m1I), in human urine. The rabbit antisera was highly specific for m1I with negligible or no inhibition by other nucleosides excreted into urine. Using the competitive ELISA, nanogram amounts of m1I were easily measured directly in urine. The assay agreed with our previous hplc analysis of m1I in urine for identifying those individuals with chronic myelogenous leukemia. Thus, this assay should greatly facilitate the quantitation of m1I as a tumor marker.
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PMID:An enzyme-linked immunosorbent assay (ELISA) for the detection and quantitation of the tumor marker 1-methylinosine in human urine. 187 11

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.
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PMID:Application of the polymerase chain reaction for detection of minimal residual disease of hematologic malignancies. 189 4

An immunohistological study of paraffin wax embedded tissue from three cases of plasmacytoid monocyte neoplasms, using a panel of antibodies which react with fixation resistant leucocyte markers, is reported. This neoplasm was found to have a distinctive antigenic profile, being negative for CD3 and elastase, but positive for CD43 and CD68. This immunological phenotype, coupled with its characteristic morphological features, should facilitate the recognition of this rare neoplasm in routinely processed tissue. Furthermore, the term "plasmacytoid monocyte sarcoma" is proposed to designate it because it is inappropriate to refer to it as a lymphoma. As all cases have been associated with a myeloproliferative disorder (usually an acute or chronic myeloid leukaemia), these tumours probably represent the accumulation in lymphoid tissue of neoplastic cells which have differentiated along the plasmacytoid monocyte pathway.
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PMID:Immunohistological diagnosis of "plasmacytoid T cell lymphoma" in paraffin wax sections. 189 Jan 95

Freshly isolated human peripheral blood lymphocytes from leukemia (AML, ALL, CML) subjects, showed a 2.5-3.5-fold increase in the poly ADPR transferase (poly ADPRT) activity whereas ovarian cancers showed a 2-fold increase. This was accompanied by a drop in NAD levels of 45%-63% in leukemia cells and 40% in ovarian cancers. Tumour promoters phorbol-12-myristate-13-acetate (PMA) and mezerein produced an increase in poly ADPRT activity in both normal and CML lymphocytes, but the increase was more marked in the case of normals. This was accompanied by a drop in NAD levels. The results presented show a marked increase in poly ADP-ribosylation in malignant cells but normal lymphocytes showed a greater response to tumour promoters as compared to CML lymphocytes.
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PMID:Enhanced poly ADP-ribosylation in human leukemia lymphocytes and ovarian cancers. 190 97

Our expanding knowledge of the immune system has provided a basis of rationality for immunotherapy. Some non-specific immunotherapy has achieved the status of standard treatment: interferon in hairy cell leukemia and chronic myelogenous leukemia, BCG in bladder cancer, and levamisole in colon cancer adjuvant therapy. Tumor infiltrating lymphocytes, moreover, offer a level of specificity heretofore unknown. Combined with the newly available synthetic cytokines that regulate the normal immune system there is the potential for a major breakthrough in biotherapeutics. Problems remain. We have yet to identify tumor antigens with the precision necessary for effective immunotherapy. Indeed, we have no assurance that tumors will regularly synthesize new antigens. In the broad spectrum of immune deficiency syndromes, we have yet to see an increase in the common epithelial tumors that account for the great bulk of human cancer. This suggests that we still have a great deal more to learn.
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PMID:Immunotherapy of cancer with lymphokines and lymphokine-activated killer cells. 192 49

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.
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PMID:The molecular pathology of chronic myelogenous leukaemia. 193 6

The human retinoblastoma gene (RB) product, which is involved in the control of cell cycle and tumor suppression, is constitutively expressed as a nuclear phosphoprotein in normal human cells. We examined leukemic cells from 22 patients with blast crisis of chronic myelogenous leukemia (CML) for alterations of the RB expression. Western blotting and flow cytometry with anti-RB-protein antibodies showed that all of five cases with megakaryoblastic crisis lacked the expression of the RB-encoded protein, whereas none of 17 cases with the other phenotypes such as myeloblastic or lymphoblastic crisis showed any abnormality. These findings suggest that megakaryoblastic transformation of CML might be lineage-specifically associated with loss of the RB protein.
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PMID:Absence of the human retinoblastoma gene product in the megakaryoblastic crisis of chronic myelogenous leukemia. 193 38

The molecular events that allow for clonal expansion of the malignant population in chronic myelogenous leukemia (CML) are poorly understood. Recent experiments in transgenic mice suggest a close temporal relationship between expression of the aberrant protein and manifestation of a hematologic neoplasm that resembles CML; tracing the same phenomenon in humans has not been possible. We studied a patient who underwent autologous bone marrow harvest after completion of chemotherapy and radiation therapy for advanced stage Hodgkin's disease. At the time of harvest his peripheral blood counts and bone marrow were morphologically normal. Sixteen months later he developed the clinical manifestations of CML. Detailed molecular evaluation of the harvested marrow showed that a small number of cells contained the Philadelphia chromosome. The time interval required for expansion of the malignant clone, as suggested by this particular patient, was at least 16 months although it is recognized that this figure may be variable.
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PMID:Duration of the preclinical phase of chronic myelogenous leukemia: a case report. 195 84

Granulocytic sarcoma is an extramedullary tumor consisting of immature cells of the granulocytic series known to occur in patients with myelodysplastic syndrome, chronic myelogenous leukemia, or acute myelogenous leukemia. This tumor may involve nodes, cervix, bone and periosteum, and infrequently the small intestine. Granulocytic sarcoma rarely occurs in the colon and has not been previously described endoscopically. We encountered a 73-year-old man with myelodysplastic syndrome who presented with fever, diarrhea, and abdominal pain. Colonoscopic evaluation (focal ulceration, friability, and nodularity) was compatible with Crohn's disease, although histology showed a dense myeloid cell infiltrate characteristic of granulocytic sarcoma. In patients with myelodysplastic syndrome or acute or chronic myelogenous leukemia presenting with diarrhea, abdominal pain, and/or fever, colonoscopy and biopsy are indicated to determine if the colon is affected by granulocytic sarcoma.
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PMID:Granulocytic sarcoma of the colon. 198 52


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