Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 59-year-old man presented with lymphocytosis with huge splenomegaly. The abnormal lymphocytes had a high nucleoplasm:cytoplasm ratio, a prominent nucleolus and hairy cytoplasmic projections. Immunophenotyping revealed B-cell leukemia with negative reactions to CD5 and CD25. Cytogenetic study showed 46,XY,der(5)t(5;6)(q35;p21), del(7)(p13)/46,idem,add(22)(q13). The patient did not respond to chlorambucil and a combination of cyclophosphamide, vincristine and prednisolone. Splenic irradiation induced partial remission. He developed progressive anemia and thrombocytopenia and died of Escherichia coli septicemia 33 months after the diagnosis of hairy cell leukemia variant.
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PMID:Hairy cell leukemia variant. 748 10

Acute myeloblastic leukemia (AML) with tetraploidy is rare. There have been only six such cases studied with banding techniques in the literature. Two were diagnosed as having AML-M2 and found to have similar near-tetraploid karyotypes with t(8;21) and missing Y chromosomes. We report two further cases of AML with tetraploid or near-tetraploid clones characterized by two t(8;21) and other chromosomal changes. Their cytogenetic findings were compatible with the diagnosis of AML-M2. Giant and bizarre blasts were seen on bone marrow (BM) smears from both cases. Immunologically, the blasts express CD2, CD15, and HLA-DR in case 1 and CD2 and CD65 in case 2. Cytogenetic studies on BM cells at diagnosis revealed that both cases had three related abnormal clones besides a normal one: 46,XY,t(8;21) (2%)/46,idem,add(7)(q31)(6.8%)/92, idem x 2 (80.6%) for case 1; and 46,XX,t(8;21)(13.4%)/47, idem,+4 (46.3%)/94,idem x 2 (39.1%) for case 2. Flow cytometric analysis displayed two cell populations in the former: one was in the diploid range and the other was in the tetraploid range. The patients did not obtain complete remissions and survived four and six months, respectively. These results indicate that tetraploid or near-tetraploid clones are secondary events which are associated with t(8;21) leukemia and may be associated with poor prognostic significance.
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PMID:Tetraploid or near-tetraploid clones characterized by two 8;21 translocations and other chromosomal abnormalities in two patients with acute myeloblastic leukemia. 895 65

The Philadelphia (Ph) chromosome is observed in approximately 1% of patients with acute myeloblastic leukaemia (AML), especially subtypes M1 and M2 in the French-American-British classification. We describe here a cytogenetic and molecular investigation of a rare case with Ph-positive AML M6 (erythroleukaemia). A 63-yr-old woman was diagnosed as having erythroleukaemia. Leukaemic cells were positive for CD4 and CD7 as well as CD13, CD33, CD34 and HLA-DR. They were analyzed by G-banding, fluorescence in situ hybridization (FISH), Southern blot and reverse transcriptase polymerase chain reaction analyses. The karyotypes at diagnosis were as follows: 61, XX, -X, -1, -2, -3, -4, -5, -7, t(9;22)(q34;q11)x 2, -15, -16, -17, -18, + 19, +21, +22 [3]/61, idem, -22, +der(22)t(9;22) [36]. FISH with BCR/ABL probes showed that 39% and 57% of interphase nuclei had double and triple BCR/ABL fusion signals, respectively. Chromosome analysis in complete remission showed a normal karyotype in all 20 metaphases, confirming the diagnosis as Ph positive-acute leukaemia. FISH at relapse showed that 92% of interphase nuclei had triple fusion signals. Rearrangement of major breakpoint cluster region (M-bcr) in the BCR gene and coexpression of p210-type (b2a2) and p190-type (e1a2) BCR/ABL fusion transcripts due to alternative splicing were also detected. We conclude that clonal evolution from double to triple Ph chromosomes may be implicated in the disease progression. Considering other two reported cases, Ph-positive erythroleukaemia appears to be correlated with coexpression of myeloid/T-lymphoid markers and hyperdiploidy with double or triple Ph chromosomes, although breakpoints in the BCR gene are heterogenous.
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PMID:Triple Philadelphia chromosomes with major-bcr rearrangement in hypotriploid erythroleukaemia. 1100 54

A 57-year-old woman was admitted to our hospital with suspected leukemia in September 1999. In 1990, systemic erythema had occurred, and mycosis fungoides (MF) had been diagnosed by skin biopsy. Interferon-gamma therapy had not been effective, and the erythema had disappeared after treatment with psoralen and ultraviolet A (PUVA) therapy (1.46 J/cm2). The patient had subsequently done well with a course of topical steroids. On admission this time, the WBC count was 1,600/microliter with 6% blasts. The total nucleated cell count in a bone marrow aspirate was 43.1 x 10(4)/microliter, of which 86.2% were peroxidase-positive blasts. Acute myelocytic leukemia (AML) was diagnosed. Chromosomal analysis demonstrated abnormalities of 48, XX, +4, +8, +add(10)(p11), add(11)(q23) in 10 of 20 cells, and 51, idem, +6, +8, +21, +mar in 8 cells with mixed-lineage leukemia gene rearrangement. Therapies (radiation, chemotherapy and PUVA) for MF, and the altered immune response seen in patients with this disease, especially in the more advanced stages, collectively termed cutaneous T-cell lymphoma (CTCL), suggest that such patients may be at increased risk of a second primary malignancy. To our knowledge, AML has been reported in 8 MF patients including the present one. Attention should be given to the possibility of MF terminating in AML.
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PMID:[Mycosis fungoides terminating in acute myelocytic leukemia]. 1107 Sep 39

We report a boy with Down syndrome and leukemia who acquired uniparental isodisomy of chromosome 7q as a secondary chromosomal change during recurrence of the disease. His karyotype before therapy was 46,XY,der(1)t(1;1)(p36;q32),-7,+21c/46,idem,del(9)(p22), whereas at recurrence it was 46,XY,der(1)t(1;1)(p36;q32,-7,der(7)(qter-->p22 through pter::q10-->qter),del(9)(p22),+21c/47,XY,+21c. By using polymerase chain reaction amplification of D7S493 and D7S527 markers, we identified the loss of the maternal chromosome 7 with a consequent paternal isodisomy in the clone with dup7q. This rearrangement could be implicated in the progression of the disease by causing (1) nullisomy for a gene or genes located on 7p22-->pter, (2) functional double doses of exclusively paternal expressed genes, and (3) restoration of the effects produced by haploinsufficiency of biparental expressed genes.
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PMID:Paternal isodisomy 7q secondary to monosomy 7 at recurrence in a Down syndrome child with acute myelogenous leukemia. 1203 27

Lineage switch from acute lymphoblastic leukemia (ALL) to acute myeloid leukemia (AML) is very rare. We report a case of a 9 yr-old ALL patient relapsed as acute myelomonocytic leukemia. At the initial diagnosis, the blast cell morphology and immunophenotype were consistent with the diagnosis of typical ALL (L1 subtype according to FAB classification). The BCR-ABL fusion gene was not found by reverse transcription-PCR. Complete remission (CR) was achieved after induction and consolidation chemotherapy (Children's Cancer Study Group 1891 protocol, CCG1891). Nine months, which is a very short time compared with other cases in the literatures, after the diagnosis of ALL, she relapsed with completely different blasts (typical AML, M4 according to FAB classification) in morphology, cytochemistry, and immunophenotyping. The karyotype has changed from 56,XY,+X,+Y,+Y,+4,+8,+10, +14,+17,-20,+21,+21,+21[6]/57,idem,+Y[19] to 46,XY,t(8;16)(p11.2;p13.1)[19]/46,XY[1], showing unrelated chromosomal abnormality to the karyotype at the initial diagnosis. Moreover, both findings were quite specific for each common cell ALL and acute myelomonocytic leukemia. These findings support that this case is completely different leukemic clones occurred at each leukemic expression. The treatment with AML 2000 protocol chemotherapy failed, and he underwent the chemotherapy with the combination of high dose cytarabine and mitoxantrone and has been in CR state for 21 months, until now.
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PMID:A case of lineage switch from acute lymphoblastic leukemia to acute myeloid leukemia. 1809 59

Two cases of therapy-related acute leukemia (TRAL) after the use of Mitoxantrone for the treatment of secondary progressive multiple sclerosis (MS) are reported. They were extracted from the group of 42 consecutive patients with TRAL diagnosed and treated in single centre between 2000-2010. They were the only two with MS and the only two treated with Mitoxantrone. The first patient was a 43-year-old male with a previous history of MS of 15-year-duration, who developed acute promyelocytic leukemia 9 months following Mitoxantrone therapy (cumulative dose 120 mg). The second patient was a 55-year-old female suffering from MS for 16 years, who developed acute mixed-phenotype leukemia, T/myeloid type, with 46,XX,del(7)(p13)[12]/47,XX,idem,+3/[6]/46,XX[2], 15 months after completion of Mitoxantrone therapy (cumulative dose 100mg). Acute mixed-phenotype leukemia, T/myeloid type is for the first time described in the context of prior Mitoxantrone therapy. Although the incidence of TRAL in relation to Mitoxantrone pretreatment is rare, we should be vigilant for the prompt identification of this adverse event.
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PMID:Therapy-related acute leukemia in two patients with multiple sclerosis treated with Mitoxantrone. 2244 Aug 94

This study was aimed to investigate the application value of the dual color dual fusion fluorescence in situ hybridization (DCDF-FISH) in BCR/ABL (+) acute lymphoblastic leukemia patients with complex chromosomal translocation. The clinical presentations of a patient with ALL were monitored regularly by bone marrow cell morphology test, chromosome analysis, flow cytometry and DCDF-FISH technique, and the reaction of patients to treatment and disease progression were dynamically observed by DCDF-FISH. The results indicated that the patient showed the typical presentation of B lineage acute lymphoblastic leukemia (B-ALL) with expression of CD10, CD19 and CD34; the chromosome analysis showed 46,XY, i(8), ider(9)t (9; 22) [23]/47, idem, +der(22) t (9;22) [7] karyotype in the bone marrow cells, FISH showed that 83% cells contained BCR/ABL fusion gene in the patient's bone marrow, among which 5% cells showed 1R1G2F signalling model, 14% cells showed 1R1G3F, and 64% cells showed 1R1G4F. The patient got complete remission when the imatinib chemotherapy combined with VTLP was carried out, and the tumor cells decreased to 19%, but the cells with 1R1G2F signal model increased to 18%. The 1R1G2F cell signal model increased up to 38% when patient relapsed. The patient died of the drug-resistance. It is concluded that the BCR/ABL (+) leukemia patient with complex translocation has multiple tumor cell subsets, and the responses of different cell subsets to the treatment are different, therefore the response to therapy and drug resistance of patient can be monitored early by the signal model of DCDF-FISH and the observation of dynamical changes of different cell subset.
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PMID:[Early monitoring drug-resistance of patients with BCR/ABL(+) ALL by DCDF-FISH]. 2459 51