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

An increasing number of papers document cases of acute leukemia in which individual blast cells co-express markers normally restricted to a single cell lineage. Numerous terms are used to refer to cases with unscheduled expression of lineage-foreign proteins; the best defined categories were hybrid acute leukemia and acute mixed-lineage leukemia. The incidence of phenotypically variant acute leukemia varies with the quality and quantity of parameters used and the stringency of the criteria employed for its definition. Considerable interest has focused on acute lymphoblastic leukemia (ALL) cells expressing one or several myeloid lineage-associated antigens (My+ ALL), CD13, CD14, CD15, CD33, and CDw65. Owing to legitimate and cryptic expression on lymphoid cells, CD11b and CD15 reagents may not be considered as specific indicators of myeloid differentiation. The reported incidence ranged from 5 to 46% in 14 studies on My+ ALL, totalling 3817 patients. Several detailed reports documented a higher incidence of My+ ALL in adults (realistically in the range 10-20%) than in children (5-10%) and in B-lineage ALL as opposed to T-lineage ALL. My+ ALL cases are more likely to display unique cytogenetic [t(9;22), 11q23, 14q32] features than My-neg ALL. There appears to be no predominant expression of a single myeloid-associated antigen among those analyzed. As the morphological diagnosis of a leukemia subtype is often imprecise, some T-neg B-neg My+ ALL cases might actually contain FAB AML-M0 populations. While the expression of myeloid-associated antigens has no apparent prognostic significance in the majority of childhood ALL subtypes, in adults myeloid antigens seem to identify a high risk group of ALL patients with a poorer response to standard ALL therapy.
Leukemia 1991 Aug
PMID:Review of the incidence and clinical relevance of myeloid antigen-positive acute lymphoblastic leukemia. 188 19

Serum ferritin concentration was studied in 136 patients with different types of acute leukemia. Pretreatment serum ferritin concentrations in the immature myeloblastic leukemia (M1 and M2 of the FAB-classification of acute leukemias) was found to be highly increased compared to the more mature types of acute myeloblastic leukemias (M3 to M5) and the acute lymphoblastic leukemias (L1 to L3). Investigation of the intracellular ferritin concentration showed, that the serum ferritin levels paralleled the intracellular ferritin concentration within the leukemic blasts. Within the immature myeloic blasts (M1) the intracellular ferritin concentration was 14-fold increased compared to normal granulocytes. This correlated with the 17-fold increased serum ferritin levels in these patients. Intracellular ferritin concentrations within the leukemic blasts of more mature types of acute leukemia (M3 to M5) were found to be only slightly increased. These data support the concept, that an increased synthesis and release of ferritin by the leukemic blasts is responsible for the increased serum ferritin concentration. This concept is also supported by the observation, that a further increase of serum ferritin concentration was seen during a cytotoxic chemotherapy. It is noteworthy, that this increase was more pronounced in the immature leukemias obviously caused by a loss of intracellular ferritin from the damaged leukemic blasts. The serum ferritin levels followed closely the activity of the disease. Increased pretreatment serum ferritin concentrations normalized completely when patients achieved complete remission. In contrast, in patients with tumor relapse or tumor progression serum ferritin concentrations increased again. These data suggest that the serum ferritin in immature myeloblastic leukemia has the characteristics of a tumor associated marker.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Ferritin in acute leukemia. Serum ferritin concentration as a nonspecific tumor marker for M1 and M2 myeloid leukemia]. 188 10

A biological hypothesis which is based upon the response of AML blast cells to retinoic acid alone and in combinations with other differentiating agents in primary culture, is proposed for the FAB classification of Acute Myeloid Leukaemias. The present biological hypothesis accounts for the biological and clinical observations in AML.
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PMID:A biological hypothesis for the FAB classification of acute myeloid leukaemias. 189 Sep 78

Leukemic cell expression and serum levels of CD4, CD8, and interleukin-2 receptor (IL-2R) were determined at diagnosis for children or adolescents with acute myeloid leukemia (AML). Cellular expression of CD4 was detected in 18 of 62 cases, CD8 in none of 60 cases, and IL-2R in one of 33 cases tested. Myeloblasts of the M4 and M5 subtypes expressed CD4 significantly more frequently than other FAB subtypes (p = 0.0001). Serum levels of the three soluble factors (tested for 91 patients) were positively correlated with each other. Increased serum CD4 levels were significantly associated with cellular CD4 expression, high leukocyte count, M5 leukemia, spleen enlargement, and age less than 1 year. High serum CD8 levels correlated significantly with splenomegaly, extramedullary disease, absence of Auer rods, and high leukocyte count. Cases with high serum IL-2R levels were less likely to have Auer rods and more likely to have splenomegaly and M5 leukemia; serum levels greater than 750 U/ml were associated with a higher probability of treatment failure (p = 0.05), even after adjustment for other potential prognostic factors. Further studies of serum CD4, CD8, and IL-2R levels may help to clarify the immunoregulatory role of T-cells in patients with AML.
Leukemia 1991 Mar
PMID:Serum CD4, CD8, and interleukin-2 receptor levels in childhood acute myeloid leukemia. 190 14

We have used genomic probes which specifically recognize DNA rearrangements of the RAR-alpha locus on chromosome 17q21 in patients with acute promyelocytic leukaemia (APL) and acute myeloid leukaemia (AML) subtypes. Molecular data were examined in comparison with morphological and immunophenotypic characterization at diagnosis in 20 hypergranular FAB M3 cases, five microgranular APL (M3v), 51 non-M3 AML and 12 myeloid CML blast crises. Rearrangements of the RAR-alpha locus were only detected in 23/25 APL cases and in none of the other FAB subtypes analysed. Surface marker characterization showed a consistent immunophenotypic profile--HLADR negative, CD9 and CD13/33 positive--in all M3 and M3v cases. Neither HLADR negativity nor CD9 positivity were associated with RAR-alpha rearrangements in non M3 AML. Our data indicate that RAR-alpha gene rearrangements are relevant diagnostic features of both M3 and M3v, and may prove useful molecular marker for follow-up analysis in APL patients.
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PMID:Rearrangements of the RAR-alpha gene in acute promyelocytic leukaemia: correlations with morphology and immunophenotype. 191 41

Bromodeoxyuridine (BrdU) was administered to 128 newly diagnosed patients with standard risk acute myelocytic leukaemia (AML) for cell cycle measurements. Labelling indices (LI) were obtained from both the bone marrow aspirate (BMasp) and biopsies (bx) and durations of S-phase (Ts) and total cell cycle time (Tc) were measured by double-labelling the S-phase cells in vitro with tritiated thymidine. Median LI BMasp was 8% and from BMbx was 25%. The median Ts was 12 h (range 3.1-35 h) and Tc was 48 h (range 11.5-211 h). All patients received induction therapy with a combination of cytosine arabinoside and an anthracycline. Outcome of therapy or FAB type were not related to cell cycle characteristics. Patients with above median LI BMasp, however, had longer remission durations (P = 0.03) as did patients with above median Ts (P = 0.03) and Tc (P = 0.03). Upon longer follow-ups, even some of the patients with slowly cycling myeloblasts have relapsed (log rank P = 0.453 and 0.203 for Ts and Tc respectively). We conclude that patients with rapidly cycling cells tend to relapse faster; however, slowly cycling nature of myeloblasts is not associated with curability.
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PMID:Biological significance of cell cycle kinetics in 128 standard risk newly diagnosed patients with acute myelocytic leukemia. 191 86

N-ras gene activation occurs via single base substitutions in codons 12, 13, and 61. We have developed a rapid screening method, termed allele specific restriction analysis (ASRA), for detection of N-ras mutations at these three critical codons in acute myeloid leukemia (AML). Patient DNA samples are amplified by the polymerase chain reaction (PCR) by using primers that induce restriction sites in normal but not mutant N-ras alleles. We have used ASRA to identify 5 point mutations in four out of 19 patients at initial presentation of de novo AML. Three patients had one mutation at codon 12, 13, or 61 respectively, while a fourth patient had concurrent mutations at codons 12 and 13. N-ras mutations were more common in patients over 65 years of age (P less than 0.04), but did not correlate with FAB classification, attainment of complete remission, disease free survival, or overall survival. ASRA can also be used as the first step in a more sensitive approach to the detection of ras mutations. When ASRA was combined with allele specific oligonucleotide (ASO) hybridization the sensitivity and specificity of these assays were increased. This allowed identification of additional low level mutations in two patients. The data presented here constitute the first complete analysis of N-ras mutations in leukemia by ASRA and include the first identification of three concurrent N-ras mutations in a single leukemic patient. By facilitating sensitive sequential studies, ASRA should contribute to our understanding of the role of N-ras mutations in leukemogenesis.
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PMID:Analysis of N-ras gene mutations in acute myeloid leukemia by allele specific restriction analysis. 195 19

We determined nine immune function parameters at diagnosis in patients with myelodysplastic syndromes (MDS) and correlated the results with the FAB classification and prognosis by univariate and multivariate analyses. Patients with refractory anaemia (RA) and refractory anaemia with ring sideroblasts (RAS) tended to have a higher CD4/CD8 ratio and a lower amount of gamma-globulins and soluble interleukin-2 receptors in serum in comparison to those suffering from the other three subgroups of MDS. FAB classification, neutrophil and CD8+ T-cell number had the best discriminatory capacity for predicting survival less than 1 year, and FAB classification, neutrophil number and serum TNF levels were predictors for conversion to acute leukaemia. The frequent occurrence of infections, on the other hand, could be better predicted by the absolute numbers of neutrophils and CD4+ cells and by the skin test score.
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PMID:Immune function parameters at diagnosis in patients with myelodysplastic syndromes: correlation with the FAB classification and prognosis. 195 86

To help understand host-tumor relationships in adult acute lymphoblastic leukemia (ALL) and to better define potential indications for interleukin-2 (IL-2) treatment in this disease, the relationship between the susceptibility of leukemia cells of 22 patients with ALL to lysis by allogeneic lymphokine-activated killer (LAK) cells and characteristics of the leukemia was studied. Lymphocytes were activated in the presence of 1000 U/ml recombinant IL-2 for 5 days. The lysis of ALL cells was studied by the release of 51Cr. The average lysis of ALL cells by control, unactivated lymphocytes was 1.2 +/- 2.4% and by LAK cells 8.9 +/- 8.6%. The susceptibility of leukemic cells to lysis did not correlate with the expression of lymphoid or myeloid differentiation markers or expression of the adhesion molecules CD54 (ICAM-1) and CD58 (LFA-3). Leukemic cells of the FAB I2 subtype were significantly more resistant to lysis than those of the other subtypes (average lysis 1.4 +/- 3.0% versus 12.3 +/- 8.2%, p = 0.003). The susceptibility to lysis did not correlate with the other initial characteristics of the leukemia. The 11 patients in whom 8% or more of leukemic cells were lysed by allogeneic LAK cells survived significantly longer than the 11 patients whose blast cells were less susceptible to lysis (p = 0.04). It is concluded that IL-2 treatment might be of benefit in adult ALL, particularly in non-L2 FAB subtypes and during complete remission to possibly delay relapse and prolong survival.
Leukemia 1991 Nov
PMID:Susceptibility of adult acute lymphoblastic leukemia blasts to lysis by lymphokine-activated killer cells. 196 Oct 38

The t(4;11)(q21;q23)-associated acute leukemia may show both lymphoid and myelomonocytic features, which suggests a pluripotent progenitor stem cell as the hematopoietic cell involved in this neoplastic process. However, there is no cytogenetic evidence to support this contention. We present a case of acute myelomonocytic leukemia (M4, FAB subtype) with t(4;11)(q21;q23), which was also found in several hypertetraploid metaphases probably corresponding to megakaryocytes. This confirms the cellular origin in an early progenitor myeloid cell of this type of acute leukemia.
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PMID:Cytogenetic evidence of involvement of an early progenitor myeloid cell in 4;11 translocation-associated acute leukemia. 198 51


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