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)

We report a female patient with Seckel syndrome who developed acute myeloid leukaemia at the age of 26 years. Analysis of bone marrow chromosomes showed an abnormal clone with abnormalities involving multiple chromosomes, including monosomy 7, trisomy 8, trisomy 11, and loss of the long arm of chromosome 5. After treatment with chemotherapy, the patient experienced severe toxicity with profound bone marrow aplasia and died of pneumonia two months later. We suggest that patients with Seckel syndrome may be at risk of developing myelodysplasia and acute myeloid leukaemia. They may also have poor tolerance to cytotoxic therapy.
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PMID:Acute myeloid leukaemia in a patient with Seckel syndrome. 818 23

As typical disorders of the elderly, myelodysplastic syndromes (MDSs) are relatively unusual in childhood. Nevertheless, up to 17% of cases of pediatric acute myeloid leukemia may have a preleukemic phase. In young patients, the goal of treatment is eradication of the preleukemic malignant clone and reconstitution of normal hematopoiesis. Allogeneic bone marrow transplantation (BMT) has proved to be capable of this, but the optimal conditioning treatment to achieve eradication remains to be defined. Between May 1989 and June 1993, eight consecutive pediatric patients with MDS received a marrow transplant from an HLA-identical, mixed lymphocyte culture (MLC) non-reactive sibling. Diagnosis at time of presentation was refractory anemia with excess of blasts (RAEB) in two patients, RAEB in transformation (RAEB-t) in three, and juvenile chronic myelogenous leukemia (JCML, the pediatric counterpart of adult chronic myelomonocytic leukemia) in the remaining three children. Conditioning regimen consisted of busulfan, cyclophosphamide and melphalan, three alkylating agents potentially capable of killing also dormant preleukemic stem cells. The preparative regimen was very well tolerated, and all patients engrafted promptly. Six out of eight patients (75%) are alive and well with a median observation time of 20 months (range 8-34 months). Serial karyotype monitoring and molecular analyses have demonstrated a full chimerism of donor cells and the complete disappearance of trisomy 8 detected before transplant in three cases. All surviving patients have a Karnofsky score of 100%. One boy, affected by RAEB-t with monosomy 7 resistant to treatment with low-dose ara-C, relapsed 11 months after BMT, evolved in AML and died from progressive leukemia. Another patient with RAEB died on day +95 after BMT due to interstitial pneumonia of unclear etiology. This study confirms that allogeneic BMT is the treatment of choice in pediatric patients with MDS, and suggests that the employed conditioning regimen is a safe and effective means for eradicating the preleukemic malignant clone. Particularly noteworthy is that the three children with JCML obtained a complete remission and one of them is now a long-term survivor.
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PMID:Busulfan, cyclophosphamide and melphalan as conditioning regimen for bone marrow transplantation in children with myelodysplastic syndromes. 818 40

Eleven patients with acute myeloid leukemia (AML) were studied with a technique that simultaneously identifies cytogenetic abnormality and immunophenotype of the same mitotic cell. To determine the cell lineages with abnormal karyotypes, monoclonal antibodies in the alkaline phosphatase-antialkaline phosphatase (APAAP) detection procedure were used. The granulocytic/monocytic lineage was involved in the leukemic process in all 11 patients. In nine patients, we also detected abnormal karyotypes in the erythrocytic and/or megakaryocytic lineages. All four patients with secondary AML showed involvement of the granulocytic/monocytic, erythrocytic, and megakaryocytic lineages into the leukemic process, as compared with five of seven patients with de novo AML. One patient with trisomy 8 showed erythrocytic participation in the leukemic process, but in another the erythrocytic lineage had only normal karyotypes. Thus, in AML, the chromosome abnormalities apparently usually originate at the multipotent progenitor cell stage, since in addition to granulocytic/monocytic lineages, erythrocytic and/or megakaryocytic lineages were also involved. Some patients show involvement of granulocytic/monocytic lineages only, however, suggesting that the target cell belongs to a more mature committed progenitor cell stage.
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PMID:Immunophenotype of mitotic cells with clonal chromosome abnormalities demonstrating multilineage involvement in acute myeloid leukemia. 822 5

We report a new case with isolated tetrasomy 8, an 82-year-old female patient in whom multiple disseminated nodular skin infiltrations up to 5 cm in diameter preceded acute monoblastic leukemia (AML-M5a). Despite an initial response to chemotherapy and radiotherapy, the patient died 1 year after diagnosis of relapsed leukemia. To assess the size of the tetrasomic clone, fluorescence in situ hybridization (FISH) analysis with a centromere-specific chromosome 8 probe was performed. Seventy percent of interphase cells showed four signals and 22% showed three signals. Because this trisomic clone was not detected by conventional cytogenetics, tetrasomic cells may have a proliferation advantage in vitro. Whether tetrasomy 8 arises from a simultaneous mitotic nondisjunction of both chromosomes 8 during one cell division or evolves secondarily from trisomy 8 through a second mitotic error is not known. Alternatively, trisomy 8 may originate from tetrasomy 8 by loss of one chromosome 8.
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PMID:Tetrasomy 8 in acute monoblastic leukemia (AML-M5a) with myelosarcomatosis of the skin. 827 52

Chromosome translocation t(15;17), the breakpoints of which are in the PML gene on chromosome 15 and retinoic acid receptor-alpha (RAR alpha) gene on chromosome 17, is specifically found in acute promyelocytic leukemia (APL). Clinically typical APL without t(15;17) and with the PML-RAR alpha fusion transcripts or rearrangements in PML and/or RAR alpha gene has been reported, suggesting submicroscopic changes at the molecular level without apparent t(15;17) or observation of normal metaphases. Trisomy 8 is common in APL as a secondary chromosomal abnormality in addition to t(15;17), as well as in acute myelogenous leukemia in general, but it is rare as a sole chromosomal anomaly in APL. PML-RAR alpha fusion transcript was detected in an APL case with trisomy 8 but without t(15;17), indicating that the leukemic cells lacked t(15;17) and still expressed the PML-RAR alpha fusion transcripts. This indicates that the same submicroscopic molecular changes as in APL with t(15;17) do occur in APL without t(15;17) and supports the use of molecular analysis for PML-RAR alpha fusion in APL.
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PMID:Detection of PML-retinoic acid receptor-alpha fusion transcripts in acute promyelocytic leukemia with trisomy 8 but without t(15;17). 829 91

Interphase cytogenetic analysis of peripheral white blood cells from a patient with acute myelogenous leukemia (AML) who was previously diagnosed with trisomy 8 was performed for the purpose of documenting clonal response to intensive chemotherapy. DNA in situ hybridization was performed using a probe specific for chromosome 8 alpha-satellite DNA sequences. Cells were stained with Wright stain prior to interphase analysis and photographed to allow correlation of cell morphology with abnormal karyotype. Prior to chemotherapy, the patient's leukocyte differential contained 8% blasts; interphase analysis revealed 23% trisomy 8 cells, including mature granulocytes. Forty days after the start of chemotherapy, at which point the patient had attained clinical remission, interphase analysis revealed only 2% cells with three signals, which was not statistically significant when compared with our own series of controls. The use of interphase FISH analysis in this case provides additional evidence that some leukemic blasts may be capable of limited differentiation in vivo and also suggests a differential sensitivity to chemotherapy between cytogenetically normal and abnormal hematopoietic precursor cells.
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PMID:Interphase FISH and morphologic analysis of AML. 833 Feb 77

Rearrangements involving chromosome 16, including inv(16) (p13q22), del(16)(q22), and t(16;16)(p13;q22), are frequent findings in acute myeloblastic leukemia (AML). Each of these rearrangements can occur as the sole karyotypic change or in association with additional chromosomal abnormalities, including in decreasing order of frequency: trisomy 22, trisomy 8, and deletion of the long arm of chromosome 7. We report a pediatric case of de novo AML, M4e subtype, with a unique combination of inv(16) (p13q22) and i(22q) occurring within the same leukemic clone. The inv(16) was detected by fluorescence in situ hybridization (FISH) analysis with two cosmid probes specific for sequences flanking the inv(16) breakpoint on the long arm of chromosome 16. Use of a chromosome-22-specific painting probe unequivocally identified a small metacentric chromosome as an i(22q). This case illustrates a variation in the association of trisomy 22 with inv(16) and suggests that duplication of the long arm of chromosome 22 may contain critical gene(s) involved in the multistep process of evolution of leukemia with 16q22 abnormalities.
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PMID:Identification of an inversion 16 coexisting with an isochromosome 22q by in situ hybridization in a case of childhood AML M4e. 841 29

Seventy-seven elderly patients (median age 72, range 59-85) with de novo AML were treated with low-dose Ara C (10 mg/m2/12 h over 21 days, for one or two courses). Thirteen (17%) achieved complete remission (CR), 16 (21%) partial remission (PR); 28 (35%) had resistant leukemia, and 20 (26%) early death or death during hypoplasia. Most (86%) of the patients had severe pancytopenia and 58% were hospitalized. Overall median survival was 3 months. Median duration of CR was 9 months. Five CR were longer than 1 year, and two were longer than 4 years. All but one PR were < or = 9 months, and 12/16 were < or = 4 months. Karnofsky index and karyotype (the latter performed for 52 patients) were the only significant prognostic factors of response to treatment (including CR+PR) and survival: poor response rate (8%) and survival (median 0.7 months) were found in patients with Karnofsky index < 60, compared with 44% and 4 months, respectively, in patients with Karnofsky index > or = 60; likewise, patients with rearrangements of chromosome 5 and/or 7 or complex rearrangements had a response rate of 13% and median survival of 1.5 months, compared with 68% and 8 months, respectively, in patients with normal karyotype or single abnormalities (not involving chromosomes 5, 7, or 8). Patients with isolated trisomy 8 had a response rate of 37% but short median survival (2.5 months). Significantly longer survival was seen in responders. Our findings suggest that, overall, low-dose Ara C yields limited results in AML in the elderly. However, it could remain a useful option in elderly patients with AML who are not candidates for intensive chemotherapy (even with the support of growth factors), provided their general condition is not too altered and they do not have an "unfavorable" karyotype (i.e., rearrangements of chromosomes 5 or 7 or complex abnormalities).
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PMID:Is there still a role for low-dose cytosine arabinoside in de novo acute myeloid leukemia in the elderly? A report on 77 cases. 850 18

Finding a clone in the bone marrow of a patient with a hematologic disorder is important to confirm the neoplastic nature of the disease and may be indicative of prognosis. Since cytogenetic analysis detects only actively dividing clones, the presence of a single abnormal cell among 20 cells analyzed raises doubts about its clonal nature. Fluorescence in situ hybridization (FISH) enables rapid detection of certain chromosomal abnormalities in metaphase and interphase cells, thus enabling detection of minor or inactive clones. Seven patients with hematologic malignancy each having random cell(s) were investigated thus: at diagnosis, with MDS and a cell with +8 (two cases) or +9 (one case) and with AML and a cell with +4 (one case), +7 (one case), or two cells with +9, +22/ +10, +17, +17 (one case). One patient with ALL in remission had one cell with trisomy 4. One patient, a male aged 66 years with refractory anemia with ringed sideroblasts, was found to have a minor trisomy 8 clone in his diagnostic marrow. A follow-up marrow 42 months later showed no trisomy 8 cell among 62 metaphases analyzed, and the percentage of trisomic cells using FISH on interphase cells was within the control range. This patient has survived for more than 42 months requiring no treatment. Single-cell abnormalities in the other six cases proved to be random events. Thus it appears that single-cell abnormalities may not be clonal or at most indicate the presence of a minor clone well below the level of cytogenetic detection. The prognostic significance of such minor clones is at present unclear.
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PMID:Single-cell trisomy in hematologic malignancy. Random change or tip of the iceberg? 878 Jul 56

The purposes of this report are to reaffirm concordance difficulties with the acute myeloid leukemia (AML) French-American-British (FAB) classification, to present the frequency of previously delineated AML syndromes in pediatric patients and to describe additional characteristic AML profiles utilizing composite morphologic, cytogenetic and immunophenotypic data. Profiles of 124 children with acute myeloid leukemia (AML) and 13 children with myelodysplastic syndrome entered on the Childrens Cancer Group (CCG) pilot study CCG-2861 were examined. Concordance between institutions and reviewers for FAB designation was 65%. Discordance was found principally between M1 and M2, M2 and M4, and M4 and M5. In 49% of marrow specimens, leukemic blasts expressed at least one T lineage-related antigen; 24% expressed the B lineage-related antigen CD19. CDw14 correlated with FAB M4 or M5 morphology and was the only surface antigen associated with a specific FAB subtype. Normal karyotypes were found for 15% of the 75 children with satisfactory karyotype preparations. Recurring aberrations, found in 76% of children, included t(15;17)(q22;q11), t(8;21)(q22;q22), inv(16)(p13q22), rearrangements of band 11q23, t(6;9) (p23;q34), trisomy 8 and monosomy 7. Results from this pilot study and from the current CCG randomized trial correlating morphology, immunophenotyping and cytogenetics, will help to classify AML into unique subgroups with differing clinical consequences or therapy requirements.
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PMID:Morphologic, immunologic, and cytogenetic classification of acute myeloid leukemia and myelodysplastic syndrome in childhood: a report from the Childrens Cancer Group. 855 38


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