Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By a colorimetric assay with dye (neutral red), the effects of recombinant human hemopoietic growth factors (rhG-CSF, rhGM-CSF, rhIL-3 and rhEPO) on the proliferation of leukemic blasts in vitro were investigated. Leukemic blasts were obtained from eight patients with acute myeloid leukemia (AML) (M1: two cases, M3: two cases, M4: four cases) and from four patients with acute lymphoid leukemia (ALL) (L2: four cases). It was shown that rhG-CSF, rhGM-CSF and rhIL-3 stimulated the blast proliferation in most cases of AML, although the degree and pattern of responses showed a striking variability in different patients. Moreover, rhGM-CSF and rhIL-3 also stimulated the leukemic blasts from some cases of ALL. No clear morphological modification providing evidence for terminal differentiation was observed when assessed by Wright stain. On the other hand, rhEPO did not have any stimulating effects on leukemic blasts in all cases. These results indicate the necessity of investigating the responses of leukemic blasts to hemopoietic growth factors in each patient prior to clinical use of such factors. For this assay, neutral red uptake method is useful because of its simplicity, rapidity, precision and convenience for handling a large volume of materials.
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PMID:Usefulness of neutral red uptake method for investigation of the effects of recombinant hemopoietic growth factors on leukemic blasts proliferation. 169 1

A new recurring chromosome abnormality was identified in 8 of 621 consecutive successfully karyotyped adults with de novo acute leukemia. These eight patients had trisomy 13 as the sole cytogenetic abnormality. On central morphologic review, five cases were classified as subtypes of acute myeloid leukemia, one as acute mixed lymphoid and myeloid leukemia, one as acute lymphoid leukemia, and one as acute undifferentiated leukemia. Blasts of all eight cases expressed one or more myeloid differentiation antigens. Three also expressed T-lineage-associated antigens; however, none of these had rearrangement of the T-cell receptor beta, gamma, or delta genes. Four of six cases tested were TdT positive. All eight patients with trisomy 13 were treated with intensive induction chemotherapy; only three entered a short-lived complete remission. Survival of patients with trisomy 13 ranged from 0.5 to 14.7 months, and was significantly shorter than that of the remaining patients (median 9.5 v 16.2 months, P = .007). We conclude that trisomy 13 is a rare, recurring clonal chromosome abnormality in acute leukemia associated with a poor prognosis. Malignant transformation of an immature hematopoietic precursor cell is suggested by the expression of antigens characteristic of both the myeloid and lymphoid lineage, the high incidence of TdT positivity, and the morphologic heterogeneity in these leukemias.
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PMID:Trisomy 13: a new recurring chromosome abnormality in acute leukemia. 169 82

Leukemic cells isolated from patients with either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL) were screened for their capacity to express the interleukin 6 (IL-6) and IL-6 receptor genes, both at the RNA and protein levels. Variable levels (10 to greater than 600 U/ml) of an IL-6 activity, inhibited by neutralizing anti-IL-6 antibodies, were detected in AML cell supernatants using the B9 cell bioassay. High levels (greater than 100 U/ml) were observed in differentiated (M4 and M5 stages) AML, as well as in less mature (M1 and M2 stages) AML. Detection of the IL-6 transcript correlated with the biological activity. In addition, both IL-6 activity and IL-6 mRNA were detected in "fresh" leukemic cells, indicating that the glycoprotein was actually synthesized in vivo. In contrast, the IL-6 gene was less frequently expressed in ALL. The IL-6 receptor gene was transcribed in both AML and ALL; binding experiments showed that the protein was present at the cell surface. The spontaneous in vitro proliferation of leukemic cells coexpressing the transcripts for IL-6 and its receptor was not significantly inhibited by a neutralizing anti-IL-6 antibody, suggesting that IL-6 is not primarily implicated in the proliferation of the leukemic clone via an autocrine loop. Synthesis of IL-6 could, however, confer on leukemic cells a selective growth advantage through activation of the cytokine cascade.
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PMID:Coexpression of the genes for interleukin 6 and its receptor without apparent involvement in the proliferation of acute myeloid leukemia cells. 171 4

A case of acute nonlymphocytic leukemia (ANLL) with primitive basophilic differentiation is presented. The patient had no antecedent history or concomitant presence of chronic myelogenous leukemia. The leukemic blasts constituted 83% of the peripheral white blood cells and more than 90% of the marrow nucleated cells. Cytoplasmic vacuoles were found in some leukemic cells. About half the leukemic cells showed a few azurophilic granules stained with Wright's stain, whereas exhibited a faint pinkish hue around the cells without cytoplasmic granules (water-soluble granules) by Riu's stain. The cytoplasmic granules failed to be stained with peroxidase but stained positively with toluidine blue. The former result could lead one to misclassify the case as lymphoid leukemia, but the characteristic finding of basophilic cells in Riu's stain should direct one to make the diagnosis of ANLL with basophilic differentiation. The cytochemical findings of this case suggested that basophilic differentiation should be considered when leukemic cells show peroxidase-negative granules. Riu's stain and toluidine blue stain are useful to make the correct diagnosis.
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PMID:Acute basophilic leukemia. A case report. 171 80

Five hundred twenty patients with de novo non-lymphocytic leukemia (ANLL) were classified according to morphocytochemical FAB criteria and then immunophenotyped using a set of 20 monoclonal antibodies (MoAb) of VI series. It was demonstrated that immunophenotyping increased the proportion of properly classified leukemias from 87% after morphocytochemical evaluation up to 97.5%. A first line diagnostic set was proposed for ANLL consisting of MoAbs detecting the following cell differentiation antigens: CDw65 (VIM2)--as a screening marker for the whole ANLL group, CD14 (VIM12)--as an indicator characteristic for M4 and M5 FAB subtypes, glycophorin A (VIEG4)--helpful in identification of erythroleukemia, CD15 (VIMD5)--which has a prognostic significance and CD41 (VIPI1)--important for identification of megacarioblastic M7 subtype. MoAbs detecting CD11b, CD61 and Ia-Dr may be used as the second line reagents.
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PMID:[Proposal of a standard set of monoclonal antibodies for differential diagnosis of acute nonlymphocytic leukemia]. 184 7

Following the observation that, besides acute myeloid leukemia cells, acute lymphoid leukemia cells of either B or T phenotype could express the transcript for the colony-stimulating factor 1 (CSF-1), a growth factor known to be restricted to the monocytic-macrophage lineage, various sources of resting and/or activated T cells and thymocytes were screened for expression of this hemopoietic growth factor. We report here that the CSF-1 transcript was rapidly (7 h) induced in T cells by a variety of stimuli, but was not detectable in either resting T cells or thymocytes. In addition, secretion of CSF-1 was detectable in the supernatants of activated T cells by 72 h, with a peak around 92-120 h. In contrast to activated monocytes, the transcript of the c-fms proto-oncogene, the product of which is the receptor for CSF-1, was not detectable in either resting or activated T cells. This observation could be relevant to the intimate relationships between T cells and antigen-presenting cells during immune responses.
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PMID:Activated but not resting T cells or thymocytes express colony-stimulating factor 1 mRNA without co-expressing c-fms mRNA. 196 39

Expression of the 93-kd tyrosine kinase encoded by the human c-fes proto-oncogene (also known as FES) is restricted to mature hematopoietic cells of the granulocytic and monocytic lineages, suggestive of a function essential to normal myeloid differentiation. However, recent studies have shown that c-fes can transform fibroblasts if sufficient levels of gene expression are achieved. These findings indicate that strict regulation of the c-fes gene is critical to normal myeloid development, whereas elevated c-fes expression may contribute to malignant transformation. In the present study, we compared the c-fes messenger RNA (mRNA) levels in leukemia blasts from patients with myeloid or lymphoid leukemia with those of peripheral monocytes from a normal donor with the use of a quantitative ribonuclease protection assay. The presence of c-fes mRNA was readily detected in both acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells, but c-fes mRNA was present in low levels or was absent in lymphoid leukemia cells. The leukemia cells of two of five AML patients and four of four CML patients expressed more c-fes mRNA than monocytes from a normal donor, with more than a threefold elevation in the cells of one CML patient. No evidence of amplification or rearrangement of the c-fes gene was detectable by Southern blot analysis of myeloid leukemia DNA, suggesting that the variation in c-fes mRNA levels are related to differences in transcriptional activity and/or message stability. These results indicate that elevated c-fes expression is a common feature of myeloid leukemia cells that could potentially contribute to the leukemia phenotype.
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PMID:Elevated expression of the c-fes proto-oncogene in adult human myeloid leukemia cells in the absence of gene amplification. 198 16

The effect of treatment with interleukin 2 (IL2) on the phenotypic and functional immune system of acute leukemia patients was investigated. Fifteen acute myeloid leukemia and acute lymphoid leukemia patients with evidence of persistent disease were further subdivided into two groups according to the percentage of bone marrow (BM) blasts: group a had 6-15% blasts and group b had 30-65%. Following two cycles of IL2 (Glaxo Imb, Geneva, Switzerland) given i.v. by continuous infusion at escalating doses, no major changes in the proportion of CD3-, CD4-, and CD8-positive cells were encountered in the blood or in the marrow of either group of patients. When these could be retested after four cycles of IL2, a significant increase of CD3+ and CD4+ cells was documented in the peripheral blood (PB), as well as a significant increase of CD3+ cells in the BM. Irrespective of the number of cycles administered, the proportion of CD16+ cells increased significantly in the blood in both groups of patients and in the marrow of group a patients only. The expression of CD25 was significantly enhanced in all samples tested. Following IL2 administration, an enhancement of the natural killer compartment was documented. This was consistently more evident in patients with more limited disease. A significant amplification of the in vitro-induced lymphokine-activated killer function was noted in the BM of the treated patients. Furthermore, we documented the presence both in the PB and in the BM of "spontaneous" lymphokine-activated killer cells generated in vivo following IL2 administration. These results demonstrate that in acute leukemia of both myeloid and lymphoid origin, treatment with IL2 is capable of inducing profound immunophenotypic and functional modifications in PB and in BM lymphocytes, particularly in patients with more limited disease. The evidence of the in vivo activation of cytotoxic cells, particularly in the BM, may help to explain the clinical responses preliminarily observed in individual acute leukemia patients.
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PMID:Peripheral blood and bone marrow immunophenotypic and functional modifications induced in acute leukemia patients treated with interleukin 2: evidence of in vivo lymphokine activated killer cell generation. 198 39

The effects of methotrexate (inhibiting dihydrofolate reductase) and nitrous oxide (inactivating methionine synthase) on intracellular folate coenzyme levels of leukemic cells were studied. Blast cells from 10 cases of acute myeloid leukemia (AML) and 5 cases of acute lymphoid leukemia (ALL) were incubated with 5 x 10(-8) M [3H] 5-formyltetrahydrofolate (5-formylTHF) for 18 h to label intracellular folate pools, which were subsequently quantitated by high performance liquid chromatography (HPLC). In AML, 5-methylTHF made up 53% of the total folate pool followed by 10-formylTHF (26%), 5-formylTHF (10%), THF (9%) and DHF (1%). Cells from ALL differed from AML (p less than 0.05) with respect to 10-formylTHF (17%) and DHF (10%). Exposure to nitrous oxide (8 h) caused an equal decrease of 10-formylTHF and 5-formylTHF in both AML (30%) and ALL (45%), whereas 5-methylTHF increased (130%). Methotrexate (4 h, 10(-6) M) caused an accumulation of DHF and a decrease of 5-methylTHF in both AML (32%) and ALL (12%). A specific reduction of the 10-formylTHF (50%) and 5-formylTHF (25%) pools was noticed in ALL. Exposure to nitrous oxide prior to methotrexate treatment aggravated the reduction of 10-formylTHF and 5-formylTHF presumably by impaired replenishment from the 5-methylTHF pool. In conclusion, this study demonstrates a significant difference in folate coenzyme distribution between cells from AML and ALL. Moreover it is shown that nitrous oxide and methotrexate treatment of leukemic cells cause an accumulation of 5-methylTHF and DHF respectively at the expense of other folate forms. The presence of substantial amounts of DHF in cells from ALL together with the specific reduction of 10-formylTHF (necessary for purine synthesis) during MTX treatment may in part explain the efficacy of methotrexate in the treatment of ALL.
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PMID:Effect of nitrous oxide and methotrexate on folate coenzyme pools of blast cells from leukemia patients. 201 7

Most cases of acute leukemia with deletions of chromosome 5q (5q-) are acute myelogenous leukemia. 5q- in acute lymphoid leukemia is rare. We studied a case of acute leukemia with 5q- using morphologic, cytochemical, immune and molecular techniques. Morphologic and cytochemical techniques were consistent with ALL (FAB L-2, PAS+, MPO-, ASD-). TdT was present. Immune studies suggested a T-cell phenotype (CD5+, CD7+); however, there was no rearrangement of the T beta-cell receptor gene. Surprisingly, the leukemia cells also expressed the CD13 myeloid antigen. Dual staining analysis showed co-expression of lymphoid and myeloid antigens on most cells. Based on these data and a review of previous reports we suggest that acute leukemia associated with the 5q- abnormality can occur in an immature stem cell resulting in a hybrid leukemia.
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PMID:Hybrid leukemia and the 5q-abnormality. 204 86


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