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)

To determine the activity of fenretinide in patients with myelodysplastic syndromes, 15 patients were treated (300 mg/d starting dose, escalated to 400 mg/d) for a 12-week course. No responses were observed in 14 evaluable patients. Exacerbation of thrombocytopenia occurred in one patient with chronic myelomonocytic leukemia, who succumbed to an intracerebral hemorrhage after 3 weeks of treatment. Two patients with long-standing stable sideroblastic anemia experienced interval leukemic progression. In one patient, clinical features of chronic myelomonocytic leukemia appeared, characterized by a striking rise in peripheral monocyte count (0.49 x 10(9)/l to 10.8 x 10(9)/l) and hepatosplenomegaly, which resolved promptly after cessation of treatment. The second patient experienced evolution into acute myelomonocytic leukemia with cytogenetic progression. The drug was well tolerated with no patient having to discontinue treatment because of toxicity. We conclude that fenretinide lacks clinical efficacy in the treatment of myelodysplasia and in some patients may enhance leukemic progression.
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PMID:Phase II trial of fenretinide [N-(4-hydroxyphenyl) retinamide] in myelodysplasia: possible retinoid-induced disease acceleration. 252 91

A girl with Fanconi's anemia developed chronic myelomonocytic leukemia and hepatocellular carcinoma. At the time that chronic myelomonocytic leukemia was diagnosed, all metaphases of the bone marrow cells revealed a chromosomal translocation involving 1p36. It is suggested that the occurrence of this rare type of leukemia in our patient is related to the chromosomal translocation.
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PMID:Chronic myelomonocytic leukemia with chromosomal changes involving 1p36 and hepatocellular carcinoma in a case of Fanconi's anemia. 254 94

Several aspects of prognosis of myelodysplastic syndromes were reviewed with special attention to refractory anemia (RA). The median survivals were 14 months in chronic myelomonocytic leukemia, 16 months in RAEB, 42 months in RA, and 58 months in RA with ring sideroblasts (RARS). Cumulative leukemia-free rates at 5 years were 31% in RAEB, 80% in RA, and 92% in RARS. The proportion of cases having very low hazards for leukemic transformation or for nonleukemic death was 92% (RARS), 73% (RA), and 26% (RAEB) for leukemic transformation and 23% (RA) and 29% (RAEB) for nonleukemic death. All RARS cases had hazard for nonleukemic death. In RA, the annual mortality rate was about 5 to 11 times higher than that of age-and sex- matched general population up to 6 years. After which no failure was found in RA cases with survival rate of 33% up to 14 years. The relative importance of hazard from leukemic transformation to nonleukemic death in RA was about one half at presentation, but this declined to less than 10% after 10 years.
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PMID:Prognosis of refractory anemias. 262 62

Criteria for the evaluation of chemotherapy for acute leukemia, chronic leukemia, Myelodysplastic syndrome and polycythemia vera were discussed. In leukemia patients the changes in the number of leukemic and normal cells are easily quantitatively evaluated. The criteria depends on the reduction and recovery of leukemic cells and normal cells. In acute leukemia because considerable parts of complete remissions ended with relapse, the evaluation seems necessarily to differentiate good remission from standard remission. For such purpose 5,000 leukocyte differential seemed effective. In the phase II study of anti-leukemia drugs, however, it seemed necessary to find efficacy less than remission, to avoid underestimation of drug efficacy because pretreated patients are usually studied in the phase II study. In the evaluation of chronic myelogenous leukemia, chronic myelomonocytic leukemia or polycythemia vera, short term judgment needs to be further studied about the correlation with longterm efficacy such as survival. The treatment of myelodysplastic syndrome is very hard to evaluate, reduction of blasts and increase of normal cells may be necessary for the improvement of symptoms. The relation of the efficacy and survival seemed necessary to be studied.
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PMID:[Evaluation of chemotherapy of hematological malignancies]. 264 5

We have examined the efficacy of various drugs in 44 patients with MDS and found the different effectiveness which depends on the type of MDS. Namely, RA appears to respond to steroid hormone, androgen, and/or vitamin D3, regardless of single or combined use. In particular, it is obvious in androgen, and as our previous reports, high content of acidic ferritin in RBC with RA have changed to more basic ones by treatment with androgen. On the contrary, these drugs were not effective on RAEB, RAEB-T, and CMML. A long-term observation is needed to determine whether the prolonged or decreased occurrence of leukemia could be obtained in the effective cases with RA. Most of the cases who did not develop overt leukemia during this study died of bleeding or infections due to thrombocytopenia or leukocytopenia, thus indicating that supportive therapies are important in patients with MDS. Since it has recently been reported that recombinant G-CSF or GM-CSF is helpful to increase the number of leucocyte and to enhance their functional recovery in MDS, these factors may be powerful agents against infections when they are carefully used with regard to the activation of leukemic clones.
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PMID:[Therapy of the preleukemic state: effect of androgens on refractory anemia]. 283 1

Type IV nuclear bodies are classified as true intranuclear inclusions that ultrastructurally contain numerous densely packed 20- to 30-nm osmiophilic granules surrounded by a microfibrillar cortex. In the present study, we have found statistically significant ultrastructural differences in the frequency and size of type IV nuclear bodies in the in vitro bone marrow fibroblastic cells (FC) derived from eight nonleukemic subjects and 13 patients with acute nonlymphoblastic leukemia (ANLL) and myelodysplastic disorders (MDD). Patients with ANLL, MDD, and myelofibrosis, as a group, had four times as many type IV nuclear bodies as nonleukemic subjects. The mean frequency of type IV nuclear bodies for patients with ANLL and MDD was 2.68% +/- 3.27% as compared with 0.63% +/- 1.06% for the nonleukemic subjects (p less than 0.05). The mean maximum type IV nuclear body area of the ANLL and chronic myelomonocytic leukemia (CMML) patients as a group was 2.08 +/- 1.10 micron2, compared with a mean maximum area of 0.93 +/- 0.10 micron2 from nonleukemic subjects (p less than 0.05). The FC were otherwise morphologically indistinguishable and displayed the typical ultrastructural features of fibroblasts. These findings have provided the first morphologic evidence that supports the concept of an altered bone marrow microenvironment in patients with ANLL and MDD. Since type IV nuclear bodies are found in high frequency in virally infected tissues, our quantitative ultrastructural findings raise the possibility of a local viral infection that affects the bone marrow microenvironment of patients with ANLL and some MDD disorders.
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PMID:Morphological evidence of an altered bone marrow microenvironment in patients with acute nonlymphoblastic leukemia and myelodysplastic disorders. 302 50

Chronic leukemias account for fewer than 5 per cent of childhood hematologic malignancies. The various subtypes are chronic mylocytic leukemia (adult, juvenile, and familial), chronic myelomonocytic leukemia chronic monocytic leukemia, and chronic lymphocytic leukemia. The most common of these, adult-type chronic myelocytic leukemia, is characterized by specific cytogenetic alterations; recent advances in molecular biology are linking these genetic events to the pathophysiology and course of this fascinating neoplasm.
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PMID:Chronic leukemias of childhood. 304 53

We treated 11 patients who had Philadelphia-chromosome-positive chronic myelogenous leukemia with natural interferon alpha (human lymphoblastoid interferon; HLBI). HLBI was given at 6-12 X 10(6) u/day i.m. or i.s.c. during induction therapy. Nine patients responded to the treatment, of whom 7 had hematologic remission and 2 had partial remission. Six patients with MDS or hypoplastic leukemia, and 3 patients with overt leukemia from MDS were treated with recombinant interferon gamma (GI-3). GI-3 was given at 0.4 X 10(6) u/m2 of body-surface area per day i.s.c. or i.v. for 4-6 weeks. In 2 patients with RAEB and hypoplastic leukemia, the blast cell count in bone marrow decreased from 8-16% to 2-3% after 4 weeks of administration. In another patient with hypoplastic leukemia, blast cells in the marrow did not decrease, but anemia was improved without transfusion, increasing the bone marrow NCC and erythroblast count. In patients with overt leukemia and CMML, no clinical effect was obtained. Interferons can therefore be offered to patients in a preleukemic state.
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PMID:[Clinical investigation of interferons in the preleukemic state (CML and MDS)]. 313 93

We describe a patient with chronic myelomonocytic leukemia who showed trisomy 8 in 100% of his bone marrow metaphases. Of interest was the finding that 20% of the Giemsa-banded metaphases also showed t(15;17)(q22;q21), with breakpoints indistinguishable from those seen in cases of acute progranulocytic leukemia (APL). The patient showed no morphologic or clinical evidence of APL, and he died after 6 months, with no evidence that the disease had progressed to acute leukemia. Although cytogenetically the breakpoints appeared to be the same as those in APL, we suspect that this patient's translocation may have differed at the molecular level from the t(15;17) commonly seen in APL.
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PMID:Chronic myelomonocytic leukemia with trisomy 8 and a related clone with trisomy 8 and t(15;17). 316 67

Members of the RAS gene family have been implicated in many neoplasms with activating mutations around amino acid positions 12 and 61. We have assessed the mutational activation of H, K, and NRAS in myelodysplasia (MDS) by polymerase chain reaction and hybridization with synthetic oligonucleotide probes. Using this method, point mutations in codons 12/13 and 61 of these RAS genes were detected in 20 of 50 patients including two with refractory anemia with ringed sideroblasts (RARS). Ten normal individuals had no detectable RAS mutations. In 11 instances, DNA from patients with detectable RAS mutations were shown to register in either NIH3T3 focus-forming or nude mouse tumorigenicity assays. In addition, one patient (RARS) was shown to have an activated NRAS gene detected by a tumorigenicity assay and Southern blot analyses. Two MDS patients had mutations detected in two different RAS genes. DNA from one of these patients was observed to give rise to transformants with activated N and HRAS. Two patients with detectable NRAS mutations in the MDS stage progressed to AML and DNA from the AML stage registered positively in a transformation assay with NRAS activation. These results show that RAS mutations can occur at early, as well as late, stages of leukemic progression. The incidence of RAS mutations appears to be significantly higher in CMML than in the other subgroups (p = 0.02).
Leukemia 1988 Aug
PMID:RAS mutations in myelodysplasia detected by amplification, oligonucleotide hybridization, and transformation. 316 76


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