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

The results of a comprehensive study on 1,000 patients who had been cytogenetically diagnosed to have leukemia in our department since 1962 are reported, and the value of cytogenetic diagnosis for leukemia emphasized. In our series, we detected patients with FAB L1 and L2 showing an abnormality rate of 60 and 66%, respectively. They included 20% with Ph1 positive ALL. In FAB L3, we found t(8;14) in 5 of the 6 patients. The FAB M1 group showed the lowest abnormality rate (50%). Forty percent of the M2 patients exhibited t(8;21), 60% of which also showed loss of sex chromosome of either X or Y. Seventy-eight percent of the M3 patients presented t(15;17) (two patients with no detectable t(15;17) showed rearrangements of retinoic acid receptor alpha gene). Inversion of chromosome 16 was found in 10% of the patients with FAB M4. Patients with M6 exhibited relatively complex chromosomes aberrations. RAEB patients showed more frequent and complex type of chromosome aberrations than PARA patients. Cytogenetic and molecular-biological analyses provided valuable information on the pathophysiology of leukemia and suggested the possible localization of novel oncogene(s).
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PMID:[The significance of cytogenetic analysis in the diagnosis of leukemia]. 177 62

Monosomy 7 as the sole cytogenetic abnormality was detected in five of 310 consecutive adult patients with acute leukaemia who were characterized by morphological, immunophenotypic and cytogenetic analyses. Morphologically, blast cells were myelomonocytic (FAB M4) in three and lymphoid (FAB L2) in two patients. By immunophenotyping, two M4 patients expressed terminal transferase (TdT) in 15-90% of myelomonoblasts (patients 3 and 1, respectively), and in the third M4 patient (no. 2), a 10% TdT+ component was present distinct from the bulk of myelomonoblasts. In one L2 patient (no. 4), the blast cells had an undifferentiated phenotype only expressing TdT and HLA-DR but lacking specific lymphoid and myeloid antigens, and patient 5 was typed as CD10+ ALL. Two patients had developed leukaemia following radiotherapy and/or chemotherapy for multiple myeloma or breast cancer. In two patients, induction chemotherapy induced a lineage switch in the immunophenotype without change in karyotype. These observations support the concept that monosomy 7 leukaemia results from the transformation of a multipotential stem cell.
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PMID:Monosomy 7 in multilineage and acute lymphoblastic leukaemia. 195 71

Myelodysplasia is an increasingly recognized complication of polycythemia vera (PCV) which often precedes leukemic transformation. This paper describes two patients with aggressive chronic myelomonocytic leukemia, previously undescribed as a complication of PCV. Both patients presented with rapidly increasing splenomegaly which was resistant to treatment with hydroxyurea and external beam irradiation. Splenectomy precipitated fatal hepatic failure in one patient. The other died shortly after transformation to acute myelomonocytic leukemia (FAB M4 classification). Pathology of the bone marrow, spleen, and liver was remarkable for extensive infiltration by dysplastic myeloid elements. Survival was short, only 4-6 months from diagnosis. The unique characteristics in these patients were: (i) prior history of PCV; (ii) rapidly increasing splenomegaly resistant to standard therapy; (iii) absence of overt marrow fibrosis; (iv) hypercellularity (greater than or equal to 90% cellular) of the bone marrow with dysplasia in the myeloid, erythroid, and megakaryocytic cell lines; (v) peripheral monocytosis greater than 1 x 10(9); and (vi) extensive infiltration of the spleen and liver by dysplastic myeloid cells. In addition, the patient who subsequently developed acute leukemia had been treated with hydroxyurea under the PVSG-08 protocol, providing further evidence of the potential leukemogenic effects of this agent.
Leukemia 1991 Jul
PMID:Chronic myelomonocytic leukemia transformation in polycythemia vera. 207 46

We studied clinical and biological features of five cases of hybrid leukemia. Three of the five patients were classified as biphenotypic leukemia because of the coexpression of myeloid/B lymphoid markers in patients 1 (FAB M2) and 2 (FAB CMMoL) and myeloid/T lymphoid markers in patient 3 (FAB M4). Patient 4 was identified as bilineal-biphenotypic leukemia because acute myelogenous leukemia (AML) (FAB M4) and acute lymphoblastic leukemia (ALL) (FAB L1) coexisted and each population coexpressed myeloid and T lymphoid markers. Patient 5 was identified as bilineal leukemia due to the conversion from AML (FAB M1) to ALL (FAB L1) at an interval of 3 months. The Philadelphia (Ph1) chromosome was negative in all cases. A leukemic blast colony formation using cell line 5637 conditioned medium as a stimulator was obtained in all four patients examined. Three of the five patients had been suffering from so-called stem cell disorders such as aplastic anemia in patient 2, trilineage myelodysplasia in patient 4 and refractory anemia with excess of blasts in transformation in patient 5. The pre-existing impairment of pluripotent stem cell was probably the background of these hybrid leukemia. Hybrid leukemia appears to have an inferior prognosis: an AML-directed chemotherapy resulted in a low remission rate (2/5) with a short duration of relapse free survival (1/2) and an ALL-directed chemotherapy produced no remission (0/3). Chronological phenotypic analysis revealed that hybrid features of leukemic blasts disappeared at the time of relapse in patient 1 and progression to AML in patient 2. Monitoring of lineage-associated markers should be required for the management of hybrid leukemia.
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PMID:Clinical characteristics of hybrid leukemia: report of five cases. 217 35

Trisomy 4 as single karyotype anomaly has recently been proposed as an acute myeloid leukemia (AML) specific aberration. Up to now, 20 cases have been reported in which the single abnormality occurred without additional chromosomal aberrations. Trisomy 4 has been found in both primary and secondary AML, the majority of cases being diagnosed as FAB M4 or M2 subtypes. In the cytogenetic analysis of 305 patients with AML, we found 209 cases with aberrant karyotypes, among them two patients (22a, male, M2; and 69a, male, M4) with trisomy 4 as single aberration. The younger patient achieved complete remission lasting 13 months and survived 22 months whereas the older patient died in aplastic phase due to septicaemia 5 weeks after admission. Trisomy 4 is proposed to be the primary aberration in both these cases of de novo AML. Although in one case, as in two cases reported earlier, cytogenetic results were only available in first relapse, we have no indication that trisomy 4 appeared in a secondary induced leukemia, because the leukemic blasts of the relapse were morphologically identical to first acute phase. In contrast to other specific chromosomal aberrations, results indicate that trisomy 4 has as yet no prognostic relevance concerning the clinical outcome.
Leukemia 1990 Mar
PMID:Trisomy 4: a specific karyotype anomaly in primary and secondary acute myeloid leukemia. 217 39

Acute myelomonocytic leukemia (M4; French-American-British classification) is light microscopically defined as the leukemia constituting leukemic cells in both granulocytic and monocytic lineages. Therefore, the characteristics of M4 have not been fully elucidated. The author previously indicated that normal neutrophilic granulocytes could be ultrastructurally differentiated from normal monocytes by the double staining of lactoferrin and lysozyme. In this investigation, the ultrastructural localization of both proteins were observed in order to make the outline of M4 clear. The leukemic cells in acute myeloid leukemia (M2) were also examined in comparison with those in M4. The leukemic cells in M4 showed the double stainability of lactoferrin and lysozyme, and the positive reactions were localized in the cytoplasmic matrix and in the granules. The staining pattern was similar to that in M2. The coexistence of lactoferrin and lysozyme in the leukemic cells in M4, which has ultrastructurally the monocytic characteristics, implied that the leukemic cells also possess the characteristics of the cells in the granulocytic lineage. This suggests that the presence of the various leukemic cells in the granulocytic lineage. This suggests that the presence of the various leukemic cells signifies the diversely abnormal maturations in vivo of the monocytes/granulocytes precursor cell and that M4 consists of not two kinds of distinguishable cells of granulocytic and monocytic lineages but various consecutive cells based on a malignant transformation of the precursor cell.
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PMID:Acute myelomonocytic leukemia: an immunoelectron microscopic study. 223 18

Reports of close associations between recurring chromosomal abnormalities and the clinical behavior of acute nonlymphocytic leukemia (ANLL) have stimulated efforts to define this disease in cytogenetic terms. Here we report on the leukemic cell karyotypes of 155 children with ANLL who were treated from 1980 to 1987 in consecutive programs of chemotherapy at this institution. Of 121 cases with adequate banding, 20% were normal, 30% had miscellaneous clonal abnormalities, and 50% were classified into known cytogenetic subgroups: inv(16)/del(16q) (n = 15), t(8; 21) (n = 14), t(15;17) (n = 9), t(9;11) (n = 9), t(11;V)/del(11q) (n = 7) and -7/del(7q) (n = 6). The inv(16)/del(16q) cases showed a nearly equal distribution of myelocytic and monocytic French-American-British (FAB) subtypes; only four of these patients presented with M4Eo morphology. Despite a 100% remission induction rate, patients with inv(16)/del(16q)-positive ANLL fared no better overall than the entire group; only 40% of this subgroup were event-free survivors at 2 years from diagnosis (P = .23). Patients with inv(16)/del(16q) frequently had CNS involvement at diagnosis (eight of 15) or initially relapsed in this site (three of eight). Event-free survival (EFS) was clearly superior for young patients with FAB M5 leukemia and the t(9;11) (P = .041). These patients were clinically indistinguishable from others with the FAB disease subtype, yet their responses to etoposide-containing therapies were noteworthy. By contrast, children with structural abnormalities involving 11q23, other than t(9;11), were infants (median age, 6 months) with FAB M4 or M5 leukemia, hyperleukocytosis, and frequent coagulation abnormalities. Patients with such changes [t(11;V) or del(11q)] relapsed early during postremission therapy: none remained disease-free more than 16 months from diagnosis. Because of resistant leukemia, patients with monosomy 7/del(7q) had a poor remission induction rate (17%; P = .0015); patients with the t(15;17) were also poor responders to induction therapy (44%; P = 0.02) because of hemorrhagic deaths. These results identify several cytogenetic subtypes of pediatric ANLL that may represent unique disease processes for which more effective early cytoreduction [-7/del(7q), t(11;V)], better supportive care measures [t(15;17)], or more effective CNS prophylaxis [inv(16)/del(16q)] would be warranted.
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PMID:Prognostic importance of cytogenetic subgroups in de novo pediatric acute nonlymphocytic leukemia. 229 13

Current views about the origin of acute lymphoid leukemia (ALL) emphasize the importance of maturation arrest at a precursor cell level. Recently, the CD22 antigen has been identified in the cytoplasm of normal bone marrow-borne immature B lineage cells, while the CD3 antigen (epsilon chain) has been detected within normal immature thymic blasts. In the first part our study performed on 100 cases of known acute leukemias, the expression of such cytoplasmic molecules, referred to as cCD22 and cCD3, was analyzed together with their appearance in the leukemic cells' membrane (mCD22 and mCD3). The presence of cCD22 in B-lineage ALL and that of cCD3 in T-ALL has indeed fully confirmed the diagnosis reached by other markers, and mCD22 and mCD3 were expressed on only a few cases of B- and T-lineage ALL, also revealing a degree of developmental asynchrony within leukemic blasts. In the subsequent analysis both cCD22 and cCD3 have been included in a standard panel of diagnostic reagents applied on 500 consecutive cases of acute leukemia. Here the aim was to analyze both the diagnostic precision of individual markers and the heterogeneity of various leukemic types in terms of the expression of membrane and intracellular antigens and their cytochemical features (Sudan Black B and esterases). It has been found that cCD22 and cCD3 are exquisitely specific for B-precursor ALL (TdT+, CD19+) and T-ALL (TdT+, CD7+), respectively, while both markers are absent in acute myeloblastic leukemia (AML) and acute myelomonocytic and monocytic leukemia (AMML/AMoL). These observations contrast the findings which demonstrate that 31% of cases among nonlymphoid acute leukemia (including AML and AMML) express CD7 and/or TdT. The study of myeloid antigens detected by CD13, CD33, and CD14 is also informative and complementary, both in diagnosing and subdividing the AML and AMML/AMoL groups. The peculiar main observation of this study is that only with the combined use of these markers in a microplate assay for membrane antigens, followed by double staining for intracellular antigens such as terminal deoxynucleotidyl transferase, cCD3, cCD22, c mu heavy chain, and T cell receptor beta, it is possible to safely establish the lineage affiliation and subgrouping of virtually all acute leukemias. Among these cases are those with aberrant combinations of markers, including 14% of B-lineage ALL (cCD22+,CD19+,TdT+) and a single case T-ALL (cCD3+,CD7+,TdT+), which exhibit CD13 and/or CD33 antigens, cases with mixtures of ALL and AML blasts, and 1.2% of acute leukemias which lack lineage affiliation and can be regarded as acute undifferentiated leukemia.
Leukemia 1989 Mar
PMID:The reliability of cytoplasmic CD3 and CD22 antigen expression in the immunodiagnosis of acute leukemia: a study of 500 cases. 246 63

Monoclonal antibodies (MoAbs) have been prepared recently that recognize the three cell-surface receptors for the Fc portion of immunoglobulin (Ig), termed Fc gamma RI (MoAb 32.2), Fc gamma R II (MoAb IV-3), and Fc gamma R III (MoAb 3G8) that are expressed on selected subsets of non-T lymphocyte peripheral blood leukocytes. In the blood, Fc gamma R I is expressed exclusively on monocytes and macrophages, Fc gamma R II on granulocytes, mononuclear phagocytes, platelets, and B cells, and Fc gamma R III on granulocytes and natural killer (NK) cells. We have examined the expression of these molecules on normal bone marrow (BM) cells and on leukemia cells from the blood and/or BM in order to determine their normal ontogeny as well as their distribution on leukemic cells. BM was obtained from six normal volunteers and from 170 patients with newly diagnosed acute leukemia. Normal BM cells were found to express Fc gamma R I, II, and III with the following percentages: 40%, 58%, and 56%, respectively. Cell sorting revealed that both Fc gamma R I and Fc gamma R II were detectable on all subclasses of myeloid precursors as early as myeloblasts. Cell sorting experiments revealed that 66% of the granulocyte-monocyte colony-forming cells (CFU-GM) and 50% of erythroid burst-forming units (BFU-E) were Fc gamma R II positive with only 20% and 28%, respectively, of CFU-GM and BFU-E were Fc gamma R I positive. Acute myeloid leukemia (AML) cells expressed the three receptors with the following frequency (n = 146): Fc gamma R I, 58%; Fc gamma R II, 67%; and Fc gamma R III, 26% of patients. Despite the fact that Fc gamma R I is only expressed on monocytes among blood cells, AML cells without monocytoid differentiation (French-American-British [FAB]M1, M2, M3, M6) were sometimes positive for this receptor. However, Fc gamma R I was highly correlated with FAB M4 and M5 morphology (P less than .001). Fc gamma R II was also correlated with FAB M4 and M5 morphology (P = .003). Cells from 11 patients with acute lymphoblastic leukemia were negative for Fc gamma R I, but six cases were positive for Fc gamma R II and III (not the same patients). These studies demonstrate that Ig Fc gamma R are acquired during normal differentiation in the BM at or before the level of colony-forming units. In addition, we show that acute leukemia cells commonly express Fc gamma R.
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PMID:Expression of the three myeloid cell-associated immunoglobulin G Fc receptors defined by murine monoclonal antibodies on normal bone marrow and acute leukemia cells. 246 4

The expression of membrane CD11c by leukaemic blast cells was examined (indirect immunorosetting) in 75 cases of acute leukaemia (myeloid, n = 60; lymphoid, n = 15) and evaluated as a potential marker for the diagnostic discrimination between monocytic (AMML-M4 and AMoL-M5) and non-monocytic (M1, M2 and M3) AML subtypes. Preliminary studies of normal bone marrow cells indicated that CD11c expression was not restricted to cells of monocytic lineage but was also present, with apparent lower density, on significant proportions of mature and immature granulocytes. Examination of acute myeloid leukaemia (AML) subtypes revealed that the non-monocytic leukaemias (n = 33) were CD11c-, defined as less than 30% positive cells, whereas all but one of the AMML-M4 (n = 13) and AMoL-M5 (n = 14) cases were CD11c+. All 15 cases of lymphoblastic leukaemia (ALL) showed less than 5% CD11c+ blasts. Membrane CD11c expression was also compared to the more widely used markers of monocytic differentiation; cytoplasmic alpha-naphthyl acetate esterase (ANAE) and membrane CD14 expression. This analysis showed that all 13 AMML-M4 leukaemias studied, including seven cases that were CD14- and eight that were ANAE-, were CD11c+. In addition, the AMoL-M5 cases (all of which were ANAE+) could be phenotypically subdivided into CD11c+ CD14+ (n = 9), CD11c+ CD14- (n = 4) and CD11c- CD14- (n = 1) subgroups. The study also confirmed that the discriminitive ability and sensitivity of the immunorosetting procedure for the detection of membrane CD11c compared favourably to immunofluorescent staining intensities as measured by flow cytometry.
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PMID:Diagnostic application of monoclonal antibody KB90 (CD11c) in acute myeloid leukaemia. 247 88


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