Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We prospectively investigated minimal residual disease (MRD) in 51 children with B-lineage acute lymphoblastic leukaemia (ALL) treated according to the Fralle 93 protocol. PCR follow-up was performed in children in morphological and cytogenetic complete remission, provided an immunoglobulin (IgH) gene rearrangement could be detected using FR 3/J(H) amplimers. MRD was studied according to our previously described methodology, with a few modifications including the use of a consensus J(H) probe to control for PCR efficiency variations. Out of the initial 51 patients, 34 were assessable for MRD at the end of induction at the time of analysis. MRD levels were as follows: > 1/10(3) in 26%, 1/10(3) to 1/10(4) in 50% and < 1/10(4) or not detectable in 24%. With a median follow-up of 20 months there were five relapses, all of which occurred in the group of patients with MRD > 1/10(3). To date, none of the patients with MRD < or = 1/10(3) (good molecular responder) has relapsed. Classification according to molecular response at the end of induction did not correlate with the conventional risks groups: there were no statistically significant differences between good and bad molecular responders. Of particular interest is the absence of correlation between WBC at diagnosis and MRD level at the end of induction. We conclude that classification of patients into good and bad molecular responders using PCR seems to be a better prognostic indicator than conventional risk factors in childhood B-lineage ALL. Patients with MRD level > 1/10(3) have a particularly poor outcome and should always be considered for alternative therapeutic strategies in the future, whereas in good molecular responders belonging to poor or intermediate risk categories, treatment de-escalation might be contemplated.
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PMID:A prospective study of minimal residual disease in childhood B-lineage acute lymphoblastic leukaemia: MRD level at the end of induction is a strong predictive factor of relapse. 923 77

In children with immune thrombocytopenic purpura (ITP), bone marrow lymphocytes can express the common acute lymphoblastic leukemia antigen (CALLA) pattern with no evidence of leukemia or lymphoma. Bone marrow lymphocytes from 23 children and 20 adults affected with ITP were studied to determine the incidence and the clinical impact of lymphocytes with the immature B-cell phenotype and CD34+ cell expression. In this investigation we identified a group consisting of 52% of the children who showed the immature B phenotype, while the remaining 48%, similarly to adult ITP displayed an increase of T-cell antigens. CD34 was positive in 53% of children, but it was present in only half of the patients with the immature B phenotype and it was always absent in adults. IgH genes disclosed a germline configuration in all six patients in the immature B phenotype group. No difference was found in the two groups of children in terms of age, presentation of the disease or final outcome. Finally, no patient in either children's group has developed an acute lymphoproliferative disorder.
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PMID:Clinical significance of HLA-DR+, CD19+, CD10+ immature B-cell phenotype and CD34+ cell detection in bone marrow lymphocytes from children affected with immune thrombocytopenic purpura. 929 67

Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of patients with B lineage acute lymphoblastic leukaemia (ALL). Two hundred and three bone marrow samples from 54 patients (33 adults and 21 children) were analysed by PCR within specific time-points after diagnosis (ie 1, 2-3, 4-6 and 7-12 months) using FR1 and JH primers (fingerprinting with a sensitivity > or =1:5 x 10[3]). CDR3-derived allele specific oligoprimers (ASO to achieve a sensitivity between 1:10[4] and 1:10[5]) were applied to 12 children and 18 adults, while size of CDR3 region, oligoclonality and background problems prevented their application to the remaining patients. All patients were followed clinically for > or =24 months. Thirty adults and 16 children presented as newly diagnosed ALL, while the remaining eight patients were analysed in first or subsequent relapse. Patients destined to relapse showed a higher proportion of positive tests (> or =50%), particularly after 1 month, than in the remission group, irrespective of age. Among patients staying in remission, a decrease in MRD-positive tests occurred during the first 12 months in both age groups. However, the proportion of positive tests dropped below 15% at a later stage in adults (4-6 months) than in children (2-3 months). Among children, only patients destined to relapse were MRD positive beyond 1 month, with the exception of only one patient, still positive at 2-3 months in the remission group. The difference in MRD positivity between relapse and remission patients was statistically significant in children (P < 0.03) at any time of testing, but only at 4-6 months in adults (P < 0.01). These data suggest that resolution of MRD in ALL occurs more rapidly in children compared to adults, particularly within the first 6 months. Children and adults, studied in first or subsequent relapse, showed a higher proportion of positive tests during reinduction compared to newly diagnosed patients.
Leukemia 1997 Oct
PMID:Molecular detection of minimal residual disease in adult and childhood acute lymphoblastic leukaemia reveals differences in treatment response. 932 95

In the search of B-cell lymphoma/leukaemia dissemination to cerebrospinal fluid (CSF), we used the highly sensitive semi-nested PCR (snPCR) for the analysis of IgH gene rearrangements. This method detects a rearranged IgH gene from a single B lymphocyte which may or may not represent the neoplastic B-cell population. We therefore performed multiple snPCR (three to five) experiments on the same CSF sample, postulating that the detection of a band of the same size and sequence in different PCR runs was highly indicative of a clonal population. 17 consecutive cases with a differential diagnosis of primary (PCNSL) (n=10) or secondary (SCNSL) (n=7) CNS lymphoma or leukaemia were investigated by the new strategy. The clonal nature of the B-cell population was confirmed in 3/10 of suspected PCNSL, and in six other cases the PCR study was indicative of reactive lymphocytosis. One case revealed a clonal B-cell population in the clinical context of an autoimmune disorder. Evidence of clonal B-cell population was found in 4/7 of suspected SCNSL. In one of these cases the detected band and its sequence proved identical to that of the primary nodal lymphoma. We believe that the evaluation of B-cell clonality in CSF requires multiple snPCR amplification on the same sample to compare the size of the products and, if necessary, the DNA sequences to ascertain the diagnosis of malignancy in equivocal cytologic and clinical findings.
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PMID:Polymerase chain reaction on cerebrospinal fluid cells in the detection of leptomeningeal involvement by B-cell lymphoma and leukaemia: a novel strategy and its implications. 935 12

The large majority of childhood B-precursor cell acute lymphoblastic leukaemia cases present IgH and TCRdelta gene rearrangements. These rearrangements have been widely used as specific markers for monitoring minimal residual disease. However, their prognostic value still remains unclear. In order to determine whether IgH and TCRdelta gene rearrangements have any influence on relapse and event-free survival (EFS), we analysed the clinical impact of these genetic characteristics in 51 B-precursor acute lymphoblastic leukaemia patients. 46/51 patients (90.2%) showed IgH gene rearrangements by Southern blot and/or polymerase chain reaction (PCR) analysis. No statistically significant associations were found between IgH gene rearrangement pattern and age, sex, WBC count, immunophenotype, risk factor, relapse or EFS. 27/41 patients (66%) showed Vdelta2Ddelta3 recombination by Southern blot and/or PCR analysis. At a median follow-up of 53 months the estimated 5-year EFS probability was 78 +/- 3% for the whole group. The EFS probability among patients with a Vdelta2Ddelta3 recombination pattern in the TCRdelta locus was 90 +/- 3%, whereas for patients without Vdelta2Ddelta3 recombination was 39 +/- 13% (P < 0.005). IgH rearrangement patterns do not appear to influence relapse or EFS probability. However, TCRdelta gene rearrangement patterns have a relevant impact on the relapse rate and the EFS probability. Patients with Vdelta2Ddelta3 recombination have better clinical outcome than patients without this recombination, independent of any other prognostic factors.
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PMID:Clinical relevance of T-cell receptor delta gene rearrangements in childhood B-precursor cell acute lymphoblastic leukaemia. 969 85

We report a largely retrospective analysis of minimal residual disease (MRD) in a cohort of 66 children suffering from acute lymphoblastic leukaemia (ALL). All patients lacked high-risk features at diagnosis, i.e. the presenting white cell count was <50 x 10(9)/l, age 1-16 years and translocations t(9;22) and t(4;11) were not present. All were treated according to either the MRC protocols UKALL X or XI. PCR of IgH, TCRdelta and TCRgamma gene rearrangements and allele-specific oligoprobing were employed for the detection of MRD. Sensitivity was at least 10(-4) in 78/82 (93%) probes examined. A total of 33 patients relapsed (seven on therapy and 26 off) and 33 remain in continuing complete remission (CCR) (median follow-up 69 months from diagnosis). Of those who remain in CCR, MRD was present in the bone marrow in 32%, 10% and 0% at 1, 3 and 5 months into therapy respectively. This is in marked contrast to the presence of MRD at these times in 82%, 60% and 41% of patients who relapsed (P<0.001, P<0.005 and P<0.005). These results provide further evidence of a strong correlation between clearance of MRD early in therapy and clinical outcome in childhood ALL.
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PMID:Minimal residual disease analysis for the prediction of relapse in children with standard-risk acute lymphoblastic leukaemia. 945 Aug 18

Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromosome 22 and ABL on chromosome 9, recombine to form a hybrid BCR-ABL gene with leukaemogenic properties. The mechanism which underlies this recombination is unknown, but additional chromosome sites may be involved to form complex BCR-ABL rearrangements. The majority of breakpoints in BCR occur within a 5 kb major breakpoint cluster region, M-Bcr. Here, we show that the 3' part of M-Bcr recombined within, or immediately adjacent to, Alu elements at the additional sites in all five complex BCR-ABL rearrangements that have been examined so far. This is a new finding which suggests that Alu sequences have an affinity for the BCR-ABL recombination process in complex rearrangements, and provides additional evidence for the association of these elements with somatic rearrangements which cause human leukaemia. We further show that sequence motifs similar to IgH switch pentamers and consensus binding sites of the lymphoid-associated Translin protein are present on one or more participating strands at 3'M-Bcr recombination sites. Motifs similar to Translin-binding sites were also identified within the Alu consensus. Expressed sequences mapped close to the breakpoint sites on other chromosomes in three of the five cases examined.
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PMID:The BCR gene recombines preferentially with Alu elements in complex BCR-ABL translocations of chronic myeloid leukaemia. 953 79

Relationship and histogenesis of Hodgkin's disease (HD) and anaplastic large cell lymphoma (ALCL) still remain unclear. Recently, Reed-Sternberg cells or Hodgkin cells in HD with B cell phenotype (B-HD) are considered to originate from germinal center B cells, ALCLs of B cell phenotype (B-ALCL) are involved in diffuse large B cell lymphoma (DLBCL) as anaplastic variant, but an origin of tumor cells of B-ALCL has not been elucidated. We have therefore investigated somatic mutation of the lg heavy chain (IgH) genes among 17 cases of B-ALCL to clarify whether there is a difference in characteristic and origin of tumor cells between B-ALCL, B-HD and DLBCL. Amplificates of IgH variable (V) region of 10 cases by the polymerase chain reaction method were sequenced and compared with reported germ line configurations. Nine cases (90%) with heavily somatic mutations were found. A case with an out-of-frame rearrangement and a case with 9 base pairs insertion were included. The mutation pattern revealed the tumor cells were selected for antibody expression and discriminated from B-HD. These findings suggest the tumor cells of B-ALCL are derived from germinal center or postgerminal center (memory and effector) B cells and an origin of B-ALCL is not different from DLBCL.
Leukemia 1998 May
PMID:Most of CD30+ anaplastic large cell lymphoma of B cell type show a somatic mutation in the IgH V region genes. 959 74

We have analysed the behaviour of minimal residual disease (MRD) after allogeneic bone marrow transplantation (allo-BMT) in 71 children with acute lymphoblastic leukaemia (ALL). The method relied on PCR of IgH, TCRdelta and/or TCRgamma gene rearrangements followed by electrophoretic size resolution and allele-specific oligoprobing. Patients were similarly conditioned; 55 received marrow from unrelated donors and 16 from related donors. MRD was assessed at various time-points up to 24 months after BMT. Three children were not evaluable due to transplant-related mortality. MRD was detected in 28/32 patients (88%) who relapsed post-BMT; 16 were positive at all times and 12 were initially negative but became positive at a median of 3 months (range 1.5-11) prior to relapse. In contrast, only eight of 36 (22%) patients who remained in continuing complete remission (CCR) (median follow-up 43 months, range 20-94) showed MRD at any time after BMT (P<0.0001). In these eight patients MRD was found up to 9 months after transplant and at low levels (0.01-0.001%). All eight (median follow-up 39 months, range 24-87) had at least two MRD-negative samples tested subsequently and five of the eight had evidence of grade I-II acute graft-versus-host disease (GvHD), raising the possibility of a graft-versus-leukaemia effect. In general, any evidence of MRD after allo-BMT is a poor prognostic sign. However, if immunotherapy were to be targeted towards patients with evidence of persisting MRD after BMT, the method described would expose only a small proportion of patients to unnecessary additional toxicity.
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PMID:Minimal residual disease status as a predictor of relapse after allogeneic bone marrow transplantation for children with acute lymphoblastic leukaemia. 972 17

In multiple myeloma (MM), allogeneic bone marrow transplantation may produce complete and durable responses, but is accompanied by significant transplant-related mortality (TRM). To assess feasibility and possible advantages offered by the use of allogeneic, growth factor-primed PBSC instead of marrow, we analyzed the data of 10 patients with MM (IgG = 6, IgA = 1, BJ = 2, non-secreting = 1; stage II = 1, stage III = 8, plasma-cell leukemia = 1) who received an allogeneic transplant with PBSC. Their age ranged between 35 and 53 years (median 45). All were HLA-identical to their sibling donors. Prior to allograft, six patients received standard-dose chemotherapy (DAV or CY-Dexa) and four a sequential intensified scheme with autologous PBSC support. At the time of transplantation, three patients were in CR, three in PR, three had refractory disease, one progressive disease. Patients were conditioned with busulfan-melphalan (n = 9) or busulfan-cyclophosphamide (n = 1), and were allografted with unmanipulated PBSC obtained by apheresis after treatment with G-CSF alone (n = 6) or GM-CSF followed by G-CSF (n = 4). All patients engrafted, with 0.5 x 10(9)/l PMN and 50 x 10(9)/l platelets on (median) day 13. Four patients had > or =grade II acute GVHD (grade II in 3, grade III in 1). Following allograft, CR was achieved in 71% patients. Eight are currently alive, with six in CR at a median of 18.5 months (range 7-28) from the transplant. Two patients died, 1 and 4 months from the allograft, respectively, and one is alive with progression. A PCR analysis of IgH rearrangement showed that residual disease was no more molecularly detectable in four out of seven evaluated patients following allograft. The results suggest that PBSC may improve the therapeutic efficacy of allogeneic transplant in MM, not only by a reduction of TRM but also by an improvement of rate and quality of response.
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PMID:Allogeneic transplantation of unmanipulated peripheral blood stem cells in patients with multiple myeloma. 973 68


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