Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 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.
 ...
PMID:Clinical significance of bcr-abl gene rearrangement detected by polymerase chain reaction after allogeneic bone marrow transplantation in chronic myelogenous leukemia. 182 68

T-cell receptor (TCR) delta gene rearrangements are observed in more than 80% of acute lymphoblastic leukemia (ALL) patients. Moreover, a preferential usage of specific genetic elements has been shown in different ALL subtypes: V delta 1 DJ delta 1 rearrangements predominate in T-ALL, while most B-precursor ALLs show a recombination of V delta 2 to D delta 3. Recently we have proposed a strategy for the detection of minimal residual disease (MRD) based on the isolation of clonospecific probes following the in vitro amplification of V delta 1 DJ delta 1 junctions by polymerase chain reaction (PCR) and now have adapted this method to the preparation of specific V delta 2 D delta 3 fragments. In the present study, clonospecific probes were generated from 11 T-ALL and 16 cALL patients (21 children, 6 adults). The sensitivity of these 27 probes in detecting residual leukemia cells varied between 10(-4) to 10(-6) as determined by semiquantitative evaluation of dilution experiments. PCR analysis of 55 bone marrow (BM) and peripheral blood (PB) samples obtained from the 27 patients during complete clinical remission showed the following results: (1) Evidence for MRD was obtained in the BM of all patients (eight of eight) investigated 2 to 6 months after remission induction and also in 6 of 11 cases on maintenance therapy 7 to 19 months after diagnosis. (2) In contrast, all patients but one (10 of 11) analyzed 6 to 41 months after the termination of treatment lacked apparent evidence for leukemia DNA; the exception was a girl exhibiting 10(-4) to 10(-5) residual cells in her PB 5.5 years after diagnosis. (3) Longitudinal analysis in nine patients disclosed marked individual differences in the intervals between achievement of clinical remission and complete eradication of the leukemia cell clone. (4) Differences in the duration of MRD were not associated with distinct clinical-hematologic features. (5) Detection of residual disease by PCR proceeded clinical relapse in two cases.
 ...
PMID:Use of polymerase chain reactions to monitor minimal residual disease in acute lymphoblastic leukemia patients. 182 78

For many years a genetic basis has been postulated for cancers and leukaemias. However, this concept has now been strengthened by the discovery of a group of genes (oncogenes) which are specifically associated with neoplasia. These genes have been identified by studies of animal oncogenic viruses, by in vitro transformation studies of mouse fibroblasts, and by molecular analyses of human tumour cells. The oncogenes are altered forms of normal genes (proto-oncogenes) whose protein products are thought to be involved in the regulation of cell proliferation. It appears that the alteration of proto-oncogenes to form oncogenes results in the inappropriate production of normal proteins or in the production of abnormal proteins. It is suggested, therefore, that the presence of such proteins would allow cells to escape from normal cell growth regulation, and as a result produce uncontrolled proliferation. Oncogene research has to date been primarily concerned with identifying oncogenes and assessing their importance in the development of a number of malignancies. Such research is therefore allowing us to build up a framework of genetic changes which define the development of each type of tumour or leukaemia. Furthermore, information concerning the oncogenes is now beginning to be applied diagnostically to help in determining predisposition of an individual to disease, in aiding the accurate staging of disease, in indicating prognosis and in developing markers to detect residual disease after therapy. It is also possible that in the future we may be able to develop new anticancer therapies, for example, based on oncogene protein inhibitors, or anti-oncogene protein antibodies or even gene therapy.
 ...
PMID:Importance of oncogene research to the cancer clinician. 182 57

Residual tumor masses are sometimes found in non Hodgkin's lymphoma (NHL) patients after chemo-radiotherapy treatment. Radiologic findings do not differentiate lymphoma from fibrosis necrotic tissue. Surgical and histology reevaluation is the most reliable method of evaluation the viability of tumor residual masses. Sixty-three consecutive high-grade NHL were treated with F-MACHOP regimen. After 3 courses of F-MACHOP the response was evaluated clinically: twenty two (36%) achieved a clinical complete remission, 32 a clinical partial remission, 7 were non responders and two were not evaluable. An early pathological response evaluation was performed in 23 clinical partial responders. Fifteen (65%) patients had no evidence of NHL after pathological restaging and were considered as pathologic complete response and completed treatment with 3 additional courses F-MACHOP. Eight (35%), histologically positive, were defined as pathologic partial response and were crossed to salvage regimens. The 1 year actuarial event-free survival differed significantly according to clinical response after 3 courses of F-MACHOP and the outcome of clinical partial responders was highly dependent on the result of pathological restaging (87% for negative and 23% for positive). Our experience suggests that a significant proportion of clinical partial responses are histologically confirmed at pathological restaging when this procedure is performed early during treatment.
Leukemia 1991
PMID:Clinical and pathological restaging in aggressive non-Hodgkin's lymphomas. 189 Aug 64

The AML model in the BN rat has contributed considerably to improved understanding of the various aspects of leukaemia growth, responses to chemotherapy, application of BMT as treatment modality and the possibilities and limitations for the detection of residual disease during the remission phase. Obviously, there are restrictions with regard to the extrapolation of the rat data to the human situation. Leukaemia growth in inbred rats is highly reproducible, while in humans it presents a high degree of individual variation. However, several characteristics are shared and the aim should be to identify the similarities as well as the dissimilarities between human and rat leukaemia. In that way progress may be envisaged with respect to reaching the final goal of curing human leukaemia.
 ...
PMID:Minimal residual disease in acute leukaemia: preclinical studies in a relevant rat model (BNML). 195 83

After induction and consolidation chemotherapy, patients with acute myeloid leukaemia (AML) usually achieve clinical remission. However, leukaemic cells, although not readily apparent, persist in most patients since the remissions cannot be sustained without further cytoreductive measures. To eradicate residual disease after induction chemotherapy, various treatment options (particularly allogeneic bone marrow transplantation) have been used. Autologous bone marrow transplantation (ABMT) can also lead to long-term survival, presumably due to the eradication or control of residual disease, but this occurs in only about 50% of cases transplanted. Relapse in the other patients occurs as a consequence of leukaemic cells surviving the conditioning regimen and/or the infusion of leukaemic cells present in the autografted bone marrow. In attempts to decrease the relapse rates after ABMT, chemical or immunological methods for in vitro purging of the harvested bone marrow cells to remove residual leukaemia have been used: the effectiveness of these procedures is unproven. This chapter describes the biology of long-term bone marrow cultures (LTBMC). How the biological differences between normal and leukaemic cells in LTBMC can be exploited to encourage the growth of normal haemopoietic cells at the expense of leukaemic cells, and how these cultured cells can be used in ABMT are discussed. The survival of patients after LTBMC/ABMT and the low relapse rate indicate that this is a useful therapeutic approach in the treatment of patients with leukaemia.
 ...
PMID:Long-term marrow cultures: in vitro purging of leukaemic cells. 195 91

Certain combinations of differentiation antigens are expressed on leukemia blasts and are absent or extremely rare among normal progenitors in the fetal liver and fetal and regenerating bone marrow. These combinations include cCD3/TdT, a thymic feature retained on thymic-acute lymphoblastic leukemia (T-ALL) blasts outside the thymus, and the coexpression of TdT and myeloid markers (CD13, CD33) on a proportion of ALL and acute myeloid leukemia (AML). Thus, double marker immunofluorescence assays are operationally leukemia-specific and can be applied in 35% of acute leukemias for detecting minimal disease at a less than 10(-4) level; only rare cases, 2 of 35 in our study, switch these relevant features during relapse. The sensitivity and specificity of these assays was tested as follows. First, bone marrow samples taken from patients who had originally presented with blasts expressing the leukemia-associated combinations but were in full morphologic remission were studied, and varying numbers (less than 0.01% to 10% of the mononuclear fraction) of cells with aberrant features were identified in 11.6% of the cases. Second, the outcome of 19 patients with minimal disease identified immunologically while in complete morphologic remission was investigated: all 19 patients have developed systemic relapse within 4 to 25 (median 14.5) weeks. In contrast, 17 of 25 patients also morphologically in complete remission and without residual disease identifiable immunologically after repeated testing are still in morphologic and immunologic remission (follow-up 17 to 114 weeks, median 28 weeks). Only eight patients in this group have relapsed so far: in two patients the relapse was localized in the cerebrospinal fluid, while in six patients a systemic relapse was observed 6 to 51 (median 21.5) weeks after the last negative immunologic bone marrow examination. In conclusion, no false-positive results were detected with these sensitive assays, and the introduction of appropriately planned prospective studies, including the immunologic detection of residual leukemia, is justified on the basis of these observations.
 ...
PMID:The immunologic detection of minimal residual disease in acute leukemia. 197 61

In this study we applied double color immunofluorescence analysis and polymerase chain reaction (PCR) amplification of rearranged TCR delta genes for detecting residual leukemia in the posttreatment bone marrow (BM) samples taken from four patients in morphological remission. In three of these patients (nos. 1-3; T-ALL) a combination of CD3 and anti-TdT antibodies (Abs) was used to identify residual blasts while in patient 4 (B lineage ALL) the combination CD13/TdT served to detect residual disease. Two rounds of PCR primed by nested amplimers were carried out to prepare clonospecific probes from presentation DNA and to investigate the follow-up samples. In patients 1 and 2 no cCD3+/TdT+ cells were seen posttreatment, but PCR amplification of the TCR V delta 1-D-J delta 1 region revealed residual disease in both patients. Patient 1 underwent allogeneic BM transplant (BMT) 8 months after diagnosis and is well 3 months post-BMT while patient 2 relapsed 12 months after presentation. In patient 3 the remission samples investigated 2 and 3 months after diagnosis did not contain cCD3+/TdT+ cells, but in the sample collected at 4 months a few such cells (0.0001-0.001%) could be detected. In the same sample, PCR amplification of the TCR V delta 2-D-J delta 1 region indicated the presence of 10(-4)-10(-3) residual leukemic cells. These findings predicted full morphological relapse which occurred 2 months later. In patient 4 CD13/TdT double positive cells were clearly seen 2 and 3 months after presentation. PCR amplification of the V delta 2-D delta 3 recombination also revealed residual blasts when applied to one of such "remission" samples. After further remission induction treatment, no immunologic evidence of residual disease was detected. This patient received an allogeneic BMT 8 months after diagnosis and is disease free 4 months after BMT. Our data indicate that both double color immunofluorescence and PCR analysis offer powerful tools to study residual leukemia and highlight the advantages as well as the potential limitations of each technique.
Leukemia 1990 Sep
PMID:The detection of residual acute lymphoblastic leukemia cells with immunologic methods and polymerase chain reaction: a comparative study. 197 35

DNA-fingerprint (DNA-F) analysis of leukemic cells can reveal new restriction fragments in some patients with acute leukemia. These genomic alterations can be used as molecular markers of residual disease. In this study, the sensitivity and clinical use of DNA-F analysis was evaluated. The detection limit for minority DNA was studied in six cell dilution series. An increasing ratio (1-20%) of cells was mixed with cells from another individual; intense extra bands could be identified in the DNA extracted from cell mixtures containing 5% of minority cells. In clinical samples from five of 19 ALL and six of 18 AML cases, the DNA-F of blast cells had new bands which could be followed during remission; in two cases the extra bands were intense enough to be detected at less than 5%. Studies of 37 patients with leukemia demonstrated that DNA-F analysis provides an additional tool for the detection of residual disease in acute leukemia.
Leukemia 1991 May
PMID:DNA fingerprinting in the detection of residual disease in acute leukemia. 203 65

Normal and aberrant immune receptor gene assembly each produce site-specific DNA rearrangements in leukemic lymphoblasts. In either case, these rearrangements provide useful clonal markers for the leukemias in question. In the t(1;14)(p34;q11) translocation associated with T cell acute lymphoblastic leukemia (T-ALL), the breakpoints on chromosome 1 interrupt the tal-1 gene. A site-specific deletion interrupts the same gene in an additional 26% of T-ALL. Thus, nearly one-third of these leukemias contain clustered rearrangements of the tal-1 locus. To test whether these rearrangements can serve as markers for residual disease, we monitored four patients with T-ALL; three of the leukemias contained a deleted (tald) and one a translocated (talt) tal-1 allele. These alleles were recognized by a sensitive amplification/hybridization assay. tald alleles were found in the blood of one patient during the 4th mo of treatment but not thereafter. Using a quantitative assay to measure the fraction of tald alleles in DNA extracts, we estimated that this month 4 sample contained 150 tald copies per 10(6) genome copies. The patient with t(1;14)(p34;q11) (talt) leukemia developed a positive assay during the 20th mo of treatment. By standard criteria, all four patients remain in complete remission 11-20 mo into treatment. We conclude that tal-1 rearrangements provide useful clonal markers for approximately 30% of T-ALLs.
 ...
PMID:Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia. 204 Jun 93


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