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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukaemic cells from 542 patients under 21 years of age with a diagnosis of acute lymphoblastic leukaemia (ALL) were typed with immunological cell surface markers between June 1975 and December 1979; 379 of these patients entered into the trials up until December 1978 have been followed for more than 1 year. They were divided into four subgroups: common (c) ALL, T (thymic) ALL, 'null' (or 'unclassified') ALL and a rare lymphoma/leukaemia type B-ALL. A T-cell phenotype was found more frequently in boys and was usually but not invariably associated with a high white cell count at presentation. A mediastinal thymic mass was present in 53% of T-ALL patients but was not observed in any unequivocal not-T ALL. Clinical prognosis differed substantially between the three major phenotypic classes, remission induction rate and remission duration being lowest in T-ALL, better in 'null' ALL, and highest in cALL (P trend less than 0 . 0001; P = 0 . 0002 for comparison of cALL versus T-ALL). There was a much higher incidence of CNS involvement in the T-ALL group than in the cALL group or 'null' All group and although this was strongly correlated with WBC count it was also significantly associated with T-ALL independent of WBC count. Overall in this series and also within the major cALL subclass there is a strong correlation between high WBC count and poor clinical response (remission induction and duration). When the three major immunological subclasses are adjusted for WBC count the prognostic correlation of antigenic phenotype is reduced and statistically insignificant. It is suggested that immunological (and enzymatic) phenotype of ALL subclasses may not be an independent correlate of prognosis but nevertheless is linked to other cell differentiation features, especially growth rate and sites of clonal expansion (e.g. marrow versus thymus), which critically influence the size of the clonogenic leukaemic population and its associated evolutionary status with the respect to drug resistant mutants at the time of diagnosis and introduction of therapy.
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PMID:Immunologically defined subclasses of acute lymphoblastic leukaemia in children: their relationship to presentation features and prognosis. 701 65

Cell cycle kinetics of childhood acute leukemia were determined by the in vitro labeling of marrow blast cells with bromodeoxyuridine (BrdUrd) and subsequent flow cytometry of BrdUrd/DNA and Ki67/DNA in 18 patients with acute lymphocytic leukemia (ALL) and eight patients with acute nonlymphocytic leukemia (ANLL). The BrdUrd-labeling index (BrdUrd-LI) and the duration of S phase (Ts) were calculated from the slope of the regression line obtained by plotting the serial labeling indices against the labeling time. The Ts and potential doubling time (DTpot) of marrow leukemia cells varied from 6.1 to 34.3 h (median 14.3 h) and 1.1 to 20.7 days (median, 7.3 days), respectively. The duration of the total cell cycle time (Tc) which was determined by the Ki-67-derived growth fraction (Ki-67-GF) varied from 14.0 to 112.5 h (median 43.2 h). BrdUrd-LI, DTpot, Ki-67-GF and Tc were significantly correlated with the subtypes (early B-ALL, T/B- ALL and ANLL) of the disease. The median values of LI and GF were much lower in ANLL than in ALL. However, the low proliferative activity of ANLL was not accompanied by a prolonged duration of the total cell cycle time. The longest median duration of Tc was noted in early B-ALL (75.2 h) and the median Tc in ANLL (36.7 h) was close to that in T/B-ALL (34 h). Ts appeared to be rather independent of subtypes of the disease. These results show that there are distinct in vitro growth characteristics in relation to the subtypes of childhood acute leukemia.
Leukemia 1995 Nov
PMID:Cell cycle kinetics in childhood acute leukemia studied with in vitro bromodeoxyuridine labeling, Ki67-reactivity, and flow cytometry. 747 84

The wt1 gene is located on chromosome 11p13 and encodes a zinc finger motif-containing transcription factor involved in regulation of growth and differentiation. Its expression was shown during embryonic development in various tissues as well as in a few human malignancies including acute leukemias. Using RT-PCR, we found wt1 gene expression in blast cells of the majority of 150 acute leukemia patients. Particularly, the wt1 transcript was detected in 12 of 14 (86%) pre-pre-B-ALL patients, in 33 of 41 (80%) cALL patients, in 23 of 31 (74%) T-ALL patients, and in 53 of 57 (93%) AML patients. Additionally, mononuclear cells from CML patients expressed the wt1 gene only when diagnosed with blast crisis. In contrast to acute human leukemias, mononuclear cells from reactive bone marrow (n = 4), and peripheral blood of healthy volunteers (n = 20), as well as normal peripheral CD34+ hematopoietic progenitors (n = 6) did not express the wt1 gene at detectable levels. Using the anti-WT1 MoAb 6F-H2 in an immunofluorescence assay on single cell level, we found the translated WT1 protein only in nuclei of leukemia blast cells but not in nuclei of normal CD34+ hematopoietic progenitor cells. Blast cells of 12 of 20 leukemia patients (60%) all tested positive for the wt1 gene expression by RT-PCR displayed a strong nuclear immunofluorescence. Its expression in the majority of human acute leukemias but not in normal mononuclear blood cells and normal CD34+ hematopoietic progenitors qualifies the wt1 gene transcript as a 'pan-acute leukemic' marker probably useful in monitoring minimal residual disease after chemotherapy and in detecting leukemic blast cells in purged or unpurged hematopoietic stem cell preparations intended to be used for autologous bone marrow transplantation.
Leukemia 1995 Jun
PMID:Presence of Wilms' tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias. 759 70

Homozygous deletions of the CDKN2 (MTS1/p16ink4) gene have been found at high frequency in cell lines derived from a variety of adult solid tumors. In order to investigate the status of the CDKN2 gene in cell lines established from childhood acute lymphoblastic leukemia (ALL), we surveyed 25 lines representing the major pediatric ALL phenotypes for the presence of this gene by Southern blot analysis. Homozygous deletions of all or part of the CDKN2 gene were detected in 21 (84%) cell lines, including 11 of 14 (79%) early-pre-B-ALL, four of five (80%) pre-B-ALL, and six of six T-ALL lines. CDN2 mRNA was detected by Northern blotting in each of the four lines containing an intact CDKN2 gene. These data suggest an important role for CDKN2 deletion in the cause and/or progression of pediatric ALL.
Leukemia 1995 Jul
PMID:Homozygous deletions of the CDKN2 (MTS1/p16ink4) gene in cell lines established from children with acute lymphoblastic leukemia. 763 Jan 90

Several lines of evidence suggest that phospholipases A2, leukotrienes and prostaglandins play a role in the proliferation of haemopoietic cells. The expression of genes involved in the biosynthesis of leukotrienes and prostaglandins was investigated in peripheral B lymphoblasts, isolated from eight patients with acute pre-B-lymphocytic leukaemia (pre B-ALL). RT-PCR analysis demonstrated that four of the investigated pre-B-ALL clones expressed the gene coding for cytosolic phospholipase A2 (cPLA2), but not the gene coding for 5-lipoxygenase. In contrast, the remaining four pre-B-ALL clones expressed 5-lipoxygenase but not cPLA2, suggesting that the transcriptional regulation of these two genes are different and that their cellular functions are not linked to each other. The capacity of pre B-ALL cells to produce LTB4 and to express the 5-lipoxygenase protein, correlated with the expression of 5-lipoxygenase mRNA. All pre-B-ALL clones expressed genes coding for 5-lipoxygenase activating protein (FLAP), leukotriene A4 hydrolase and prostaglandin (PG)H synthase 1. Seven of the eight pre B-ALL clones expressed PGH synthase 2. In comparison, normal tonsillar B cells did not express cPLA2 or PGH synthase 2.
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PMID:Diverse expression of cytosolic phospholipase A2, 5-lipoxygenase and prostaglandin H synthase 2 in acute pre-B-lymphocytic leukaemia cells. 764 98

To get more insight into the phenotypic changes of childhood acute lymphoblastic leukemia (ALL) at relapse, a detailed morphological and immunophenotypic study in 40 childhood ALL cases (32 precursor B-ALL and 8 T-ALL) was performed. Expression patterns of non-lineage specific markers (terminal deoxynucleotidyl transferase (TdT), CD34, and HLA-DR), B-lineage markers (CD10, CD19, CD20, and CD22), T-lineage markers (CD1, CD2, CD3, CD4, CD5, CD7, and CD8), and cross-lineage myeloid markers (CD14, CD15, and CD33) were compared at diagnosis and relapse. In case of low blast counts (< or = 70%) at relapse, double labeling for membrane markers and TdT was used in order to define the precise immunophenotype of the TdT+ leukemic cells. An immunological marker-shift was defined as either a conversion from positive to negative and vice versa or a difference in positivity of > or = 50%. Morphological differences between diagnosis and relapse were detected in 34% of precursor B-ALL and 14% of T-ALL. Differences in immunological marker expression were found in 72% of precursor B-ALL and in 75% of T-ALL, and generally concerned minor shifts with loss or acquisition of a few markers. The morphological shifts and immunophenotypic shifts were not correlated. Immunophenotypic shifts were found for all markers tested in precursor B-ALL, except for HLA-DR. Shifts in CD10 expression (16% of cases) were only observed in relapses occurring 30 months or more after diagnosis. In four precursor B-ALL an intra-lineage shift was found at relapse (one common ALL to null ALL and three pre-B-ALL to common ALL or null ALL) and two precursor B-ALL cases were diagnosed as acute non-lymphocytic leukemia at relapse based on morphology and immunophenotype. In T-ALL, neither intra-lineage nor inter-lineage shifts were observed, although shifts were detected in all T cell markers tested, except for the lineage specific CD3 and T cell receptor (TcR) markers. In conclusion, immunophenotypic shifts at relapse frequently occur in precursor B-ALL and T-ALL, in a small percentage leading to an intra-lineage shift (10%) or inter-lineage shift (5%). Therefore immunophenotypic monitoring of minimal residual disease in ALL patients should be based on multiple marker combinations, preferably together with polymerase chain reaction analysis of rearranged immunoglobulin and/or TcR genes or chromosome aberrations.
Leukemia 1995 Sep
PMID:Immunophenotypic changes between diagnosis and relapse in childhood acute lymphoblastic leukemia. 765 22

In 91 of 106 adult patients with acute lymphoblastic leukemia (ALL) enrolled in the treatment protocol ALL HOVON-5 between May 1988 and October 1991, the immunophenotype of the leukemia was determined and correlated with clinical characteristics at presentation. The immunological marker analysis was performed in ten laboratories, all members of the Dutch Study Group on Immunophenotyping of Leukemias and Lymphomas (SI-HON). Undifferentiated blasts were found in four patients, 67 had B-lineage ALL, 18 had T-lineage ALL, and two had biphenotypic ALL. The age of T-lineage ALL patients was lower (mean 29.3) than that of B-lineage ALL patients (mean 35.5). Tumor mass, as expressed by leukocyte count, organomegaly, and LDH, was more pronounced in T-lineage ALL. Hemoglobin and platelet count was similar in all (sub)types. CD34 was expressed in 58% of the leukemias, but most frequently in the common B-ALL (70%). Thirteen percent of the leukemias expressed one or more markers not associated with their lineage. In this prospective study immunological data were not evaluable for 15 patients. On four of them data were not available because of dry tap, for six patients the typing was technically insufficient, and for four patients the results were unclassifiable; with one patient the marker analysis was not performed.
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PMID:Acute lymphoblastic leukaemia in adults: immunological subtypes and clinical features at presentation. 768 3

The accumulation of intracellular cytosine arabinoside-5'-triphosphate (Ara-CTP) is determined in five lymphoblastic cell lines: Molt 4, H9 and three newly established cell lines from paediatric patients, KFB-1, KFB-2, KFT-1. The cell lines KFB-1 and KFB-2 are B-lymphoblastic (B-ALL), the others are T-lymphoblastic leukaemic cells (T-ALL). The Ara-CTP levels were compared with the sensitivity of the cells to Ara-C. The cells were incubated at different concentrations (100 nM-100 microM) of Ara-C for 4 h or incubated for variable times (30 min-11 h) at 0.1, 1 and 10 microM Ara-C to form Ara-CTP. The Ara-CTP-concentrations were measured by high pressure liquid chromatography (HPLC). To determine the sensitivity of the cells to Ara-C, the MTT colorimetric-assay was used. The studies indicate that different B- and T-lymphoblastic leukaemia cell lines accumulate Ara-CTP to a markedly different extent. Ara-CTP plateau levels and sensitivity of the cells to Ara-C correlated well in four of the five cells lines studied.
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PMID:Formation of cytosine arabinoside-5'-triphosphate in different cultured lymphoblastic leukaemic cells with reference to their drug sensitivity. 771 27

The t(1;19)(q23;p13) translocation occurs commonly in B-lineage ALL. Previous reports have demonstrated a predominance of cases with expression of cytoplasmic Ig mu (C mu+), and FAB L1/L2 phenotype, a poor prognosis and expression of a fusion transcript involving the E2A and PBX1 genes in C mu+ but not in C mu- cases. Of 38 patients with karyotypically proven t(1;19) (q23;p13) leukaemias, we extensively analysed 18 patients with acute leukaemia including 16 B-lineage ALLs, one T-ALL and one AML M4. The AML was associated with a classic E2A-PBX1 fusion transcript and may represent the human counterpart of the AMLs induced by E2A-PBX1 retroviral infection of murine marrow progenitors. The T-ALL was E2A-PBX1 negative and neither the E2A nor the LYL-1 genes, both situated at chromosome 19 p13, were rearranged. Of the 16 B-lineage ALLs, four had cytological features resembling an 'L3-like' phenotype classically associated with Burkitt's lymphoma, two at diagnosis and relapse and two exclusively at relapse. E2A-PBX1 fusion transcripts were detected by RT-PCR in all 13 C mu+ patients and in 2/3 C mu- cases. The 'L3-like' phenotype did not correlate with a particular stage of maturation arrest (one sIg+, one C mu+, one C mu-) or type of E2A-PBX1 transcript, but was associated in all cases with a trisomy 8. Translocation, rearrangement, amplification or over-expression of the c-myc gene was not observed in these cases, demonstrating that the apparent association with trisomy 8 is not due to deregulation of this gene. We therefore show that the E2A-PBX1 transcript, although occurring predominantly in C mu+ pre-B ALL, also occurs in C mu- early pre-B ALL, sIg+ B-ALL and even in AML. These results suggest that the stage of maturation arrest, and indirectly the prognosis, are not solely due to the type of fusion transcript associated with the t(1;19).
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PMID:Heterogeneity of t(1;19)(q23;p13) acute leukaemias. French Haematological Cytology Group. 773 49

The chromosomal translocation t(1;19)(q23;p13) and its variant form der(19)t(1;19) found in 3-5% of acute lymphoblastic leukemia (ALL) results in the expression of the E2A-PBX1 fusion transcript. Although strongly associated with a pre-B immunophenotype, we report the occurrence of t(1;19) in bone marrow or peripheral blood in nine patients with ALL with the following immunophenotypes: pre-B ALL (four), c-ALL (two), c-ALL clg not tested (one), null-ALL (one) and mature B-ALL (one). The E2A-PBX1 fusion transcript investigated by reverse-transcriptase polymerase chain reaction (RT-PCR) was seen in all patients at diagnosis and/or on follow-up samples. Six patients are alive in first clinical remission. Of these patients, three were PCR+ve from between 2 and 38 months from diagnosis, and three were PCR-ve when examined at 5, 26 and 51 months from diagnosis. Two patients are in second remission. One was PCR+ve at 18 months, suffered a CNS relapse at 21 months but was PCR-ve 1 month later. The other was PCR+ve in remission at 2 and 11 months from diagnosis and in testicular relapse at 31 months, but was PCR-ve 5 months later. The remaining patient died 2 months from diagnosis and was not investigated in remission. The prognostic significance of these findings remains to be investigated.
Leukemia 1995 May
PMID:Expression of the E2A-PBX1 fusion transcripts in t(1;19)(q23;p13) and der(19)t(1;19) at diagnosis and in remission of acute lymphoblastic leukemia with different B lineage immunophenotypes. 776 44


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