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)

Clonality, in MDS, can only be assessed in patients with chromosomal rearrangements or in females heterozygote for X chromosome restricted polymorphisms. "Illegitimate" rearrangements of the immunoglobulin heavy chain (IgH) gene and incomplete rearrangements involving V delta 2 and D delta 3 segments of the T-cell receptor delta (TcR delta) gene are seen in some cases of AML, and AML post-SMD, and can be detected by a sensitive PCR method. In order to analyse clonality in additional cases in MDS, we looked for Ig H and TcR delta gene rearrangement by PCR in 95 cases of MDS. A rearrangement of the Ig H gene was seen in 2 of the 95 patients: in the circulating blood of 2 of the 36 cases of chronic myelomonocytic leukaemia (CMML) and in none of the marrow samples of the other 59 MDS. A rearrangement of the TcR delta gene (involving V delta 2 and D delta 3 segments) was seen in three cases (in the circulating blood of two other CMLL patients, and in the bone marrow of another MDS patient). Twenty-five of the 90 cases of MDS with negative PCR findings, in addition to the five cases with positive PCR findings underwent Southern blot analysis of Ig H and TcR delta genes, and PCR analysis of V delta 1 and J delta 1 segments of the TcR delta gene. Those examinations were normal in all the cases tested. In patients with positive PCR findings for Ig H or V delta 2 D delta 3 rearrangements, the proportion of rearranged cells was evaluated at 1-5% in four cases, and 5-10% in the remaining patient. Because the analysis was performed on total circulating leukocytes or total nucleated marrow cells, the nature of the clonal population in positive cases (lymphoid cells? myeloid cells? blasts?) could not be determined. From a practical point of view, Ig H and TcR delta gene rearrangements seem to very rare in MDS, and cannot be used as clonality markers in most cases.
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PMID:Immunoglobulin and T-cell receptor delta gene rearrangements are rarely found in myelodysplastic syndromes in chronic phase. 818 27

We treated a 16-month-old girl with myelodysplastic syndrome (MDS; refractory anemia with excess of blasts subtype, RAEB by FAB classification) that developed into acute megakaryoblastic leukemia (ANLL-M7). The blast cells were positive for CD41 shown by flow cytometry and for platelet peroxidase by electron microscopy. Cytogenetically, five kinds of abnormal karyotypes were apparent at the initial visit and karyotypic progression (clonal evolution) was also evident. These karyotypes were considered to be derived from the putative original clone, 48,XX, +6, +21. The observed karyotypes were considered 50,XX, +4,add(4)(q31), +6,add(7)(p22),add(10)(q24),add(12)(q11), +20, +21, + mar[karyotype A];48,XX,add(4)(q31), +6,add(10)(q24),add(12)(q11), +21 [karyotype B];48,XX, +6,t(6;13)(p23;q14), +21 [karyotype C];51,XX, +X, t(6;13)(p23;q14), + der(6)t(6;13)(p23;q14), +21, +21, + mar [karyotype D]; and 49,XX, +X, -3,t(6;13)(p23;q14), +der(6)t(6;13)(p23;q14), -12, +21, +21, + mar [karyotype E]. It seems karyotypes B and C were derived from the putative clone; karyotype B developed into karyotype A; and karyotype C developed into karyotype E through karyotype D. After development of ANLL-M7, the cytogenetic study showed a karyotype with further karyotypic progression. The patient was treated with high-dose cytosine arabinoside (HD AraC) followed by allogeneic bone marrow transplantation. Despite intensive care, she died 3 months after the transplantation.
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PMID:Childhood myelodysplastic syndrome with clonal evolution progressing to acute megakaryoblastic leukemia (ANLL-M7). 822 7

A second case of acute myeloid leukemia (AML) with a t(2;4)(p23;q25) as the sole anomaly is reported. Our case had a de novo AML (M2); the case previously described had AML (M2) post-MDS. It is suggested that t(2;4)(p23;q25) is a new, recurrent, but rare anomaly in AML.
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PMID:Translocation (2;4)(p23;q25): an additional case of a new recurrent anomaly in acute myeloid leukemia. 824 96

p53 overexpression was studied immunohistochemically in paraffin-embedded bone marrow biopsies using a recently described technique for antigen retrieval based on microwave oven heating of paraffin sections. Using a monoclonal antibody (PAb1801) that reacts with human cellular p53, nuclear staining was detected in 7/11 (63%) therapy-related myelodysplastic syndromes and in 3/4 (75%) therapy-related acute myeloid leukemias. Conversely, staining for p53 was seen only in 9/40 (22%) cases of "primary" hematologic conditions (P < 0.007); these included myelodysplastic syndromes [#2], acute myeloid leukemia [#4], and chronic granulocytic leukemia in accelerated phase or blast crisis [#3]. Biopsies of normal controls and of chronic granulocytic leukemia in stable phase were consistently p53(-). Nine of the 10 karyotyped p53(+) acute myeloid leukemia/myelodysplastic syndrome cases showed complex cytogenetic findings with frequent involvement of chromosome 5 and/or 7. Only four of the 33 karyotyped p53(-) cases showed similar cytogenetic changes. Chromosome 17 involvement was present in four of 13 (31%) cytogenetically assessed p53+ cases, but in none of the p53(-). In univariate analysis, p53 expression in both MDS and AML was significantly associated with shorter survival. The frequent overexpression of p53 in therapy-related myelodysplastic syndromes, therapy-related acute myeloid leukemias and in accelerated phase/blast crisis, chronic granulocytic leukemia and its strong association with complex karyotypes suggests an important role of this gene in the pathogenesis of these leukemic conditions.
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PMID:Frequent p53 overexpression in therapy related myelodysplastic syndromes and acute myeloid leukemias: an immunohistochemical study of bone marrow biopsies. 824 7

Therapy-related acute myeloid leukemia (t-AML), often presenting as myelodysplasia (t-MDS), has become the most serious long-term complication of cancer therapy and offers a unique opportunity to study chemical leukemogenesis. Seven cohorts of patients treated for six different types of primary tumor have been followed closely for leukemic complications, and 115 consecutive patients with t-MDS or t-AML, including 45 cases from the cohorts, have been investigated cytogenetically at our institutions during the past 16 years. In patients primarily treated with alkylating agents, the risk of t-MDS and t-AML increased by approximately 1% per year from 2 to at least 8 years after start of treatment. In most cases, the disease presented as t-MDS with loss of a whole chromosome 5 or 7, or various parts of their long arms, and the leukemias were of FAB-subtypes M1, M2, or M4. In patients treated with drugs targeting at DNA-topoisomerase II, such as etoposide, doxorubicin, 4-epidoxorubicin, or mitoxantrone combined with drugs reacting directly with DNA, such as cisplatin or alkylating agents, the risk of leukemia increased much more steeply from only one year after start of therapy. These early onset cases often presented as overt leukemia of FAB-subtypes M4 or M5 with balanced translocations to chromosome bands 11q23 and 21q22, whereas later onset cases often shared characteristics with cases observed after therapy with alkylating agents alone. Both alkylation of DNA and poisoning of DNA-topoisomerase II may result in development of t-AML with different clinical and cytogenetic characteristics. There may be a synergistic leukemogenic effect between the two types of drug, and in patients with germ cell tumors treated with etoposide, cisplatin and bleomycin, reassessment suggested the risk of leukemia to increase exponentially with increasing doses of cisplatin and etoposide.
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PMID:Therapy-related myelodysplasia and acute myeloid leukemia. Cytogenetic characteristics of 115 consecutive cases and risk in seven cohorts of patients treated intensively for malignant diseases in the Copenhagen series. 825 96

Owing to recent technical developments in automated hematology analyzers, identification of 5-part differential counts in white blood cells and also of abnormal leukocytes has become possible. Blood specimens from 200 patients with leukemic hematologic conditions were processed through a Coulter STKS which gives a favorable white cell differential count utilizing the following parameters: volumetric impedance (V), electric conductivity/cell volume (C), and a monochromatic laser beam which provides collectively white cell scatterplot (S). To analyze the presented figures of a pathologic scatterplot (SP) on the visual display unit, the standard scale derived from 220 normal SP patterns which was composed of four kinds of cell SP scales (neutrophil: N, monocyte: Mo, eosinophil: Eo, lymphocyte: Ly) was applied. Leukemic SP figures were variable depending upon both the type of FAB classification and their therapeutic processes. SP forms of M0-blasts were semi-round and located in the central area surrounded by N-, Mo-, and Ly-SP scale. Blast SP of M1 and M2 was shown as a developing process to the SP field containing immature myeloid cells extending from the central area. It was reasonable that immature neutrophilic SP expression was obtained in M3 and Ph1 positive CML. However, the SP of M3v and Ph1 negative CML showed myelomonocytic features as CMMoL does. Typical myelomonocytic SP patterns were obtained in M4 patients. SP figures of MDS were characterized by deformability, dislocation and another abnormality, and these changes, especially in lymphocytes are very useful for diagnosis of MDS. Therefore, the FAB subtype of AML including MDS and CML could be distinguished from each other on the basis of SP pattern. In lymphoproliferative disorders, limited conductivity in ALL-SP was characteristic, while irregular and deformed SP was peculiar in leukemic malignant lymphoma. It would be a valuable process to analyze the SP pattern obtained from an automated hematology analyzer for identification of leukemic diseases.
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PMID:[Hematological analysis of leukemic diseases using an automated hematology analyzer]. 829 37

Three cases of secondary (therapy-related) hematologic malignant conditions were identified among 95 children as old as 18 years of age; the cases were diagnosed between 1984 and 1990 and consisted of acute lymphoblastic leukemia, acute myeloid leukemia (AML), and myelodysplastic syndrome (MDSs). They constituted 10% of all new cases of AML and MDS seen at the University Hospitals of Cleveland during this time and were not related to congenital factors. The primary malignant conditions were malignant thoracopulmonary tumor (Askin tumor), neuroblastoma, and Burkitt's lymphoma. The secondary hematologic disorders all showed a prominent monocytic component: acute monocytic leukemia, MDSs evolving to acute myelomonocytic leukemia, and chronic myelomonocytic leukemia. The mean interval between treatment for the primary malignant condition and the onset of secondary disease was 36 months. All had received cyclophosphamide and an epipodophyllotoxin for the primary tumor; two were treated with radiation therapy. Cytogenetic abnormalities included del(5), del(13), t(1;6), and t(9;11)(p22[symbol:see text]3). The survival time after the onset of secondary disease was short.
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PMID:Myelodysplastic syndrome and acute myeloid leukemia after treatment for solid tumors of childhood. 837 35

The recovery of colony-forming cell numbers after curative treatment for leukemia and severe aplastic anemia (SAA) was studied. We examined 191 patients (85 acute myeloid leukemia [AML], 48 acute lymphocytic leukemia [ALL], 32 chronic myeloid leukemia [CML], 17 SAA, and nine myelodysplastic syndrome [MDS]) who were in hematologic remission 6 months to 13 years after either curative chemotherapy (n = 69) or allogeneic bone marrow transplantation (BMT) (n = 122) by culturing their precursor cells from bone marrow (BM) (n = 548) and peripheral blood (PB) (n = 529) in methylcellulose. Thirty-six BM donors and 25 PB donors served as controls. BM colony-forming cell numbers were abnormally low in all patients (p < 0.002) irrespective of underlying disorder and type of treatment (chemotherapy or irradiation). These numbers did not normalize with time--colony-forming cells were still strongly reduced up to 10 years after therapy, whether or not the patient had received an allogeneic bone marrow graft (p < 0.002). We also compared patients who remained in stable hematologic remission with those who later relapsed (6 months to 2 years after treatment). BM colony-forming cell numbers were significantly lower in patients who subsequently relapsed (p = 0.004). In contrast to BM cultures, we found normal colony-forming capacity by PB precursors in all patients. We conclude that (1) after chemotherapy or BMT, colony-forming cell numbers of BM in culture are permanently reduced; (2) this defect is probably due to a dysfunction of the BM environment rather than to a numerical reduction of the precursor cell pool; and (3) very low colony-forming capacity may be related to relapse.
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PMID:Colony growth in cultures from bone marrow and peripheral blood after curative treatment for leukemia and severe aplastic anemia. 840 33

The DNA content of bone marrow cells in patients with acute leukemia preceded by a myelodysplastic stage (MDS-AML) was compared to that in patients with de novo AML. We studied granulocytes, lymphocytes, monocytes, and blasts/promyelocytes from Feulgen-stained bone marrow smears of 11 patients with de novo AML, ten patients with MDS-AML, and 13 apparently healthy controls. The mean amount of DNA per cell (DNA index; DI) in each cell population was determined using a digital video-based image-analyzing system (CAS-100). Analysis of variance (F test) showed a significant difference in the DNA content between de novo AML on one hand and MDS-AML and controls on the other as regards to blasts/promyelocytes (P < 0.01), lymphocytes (P < 0.05), and monocytes (P < 0.01), respectively. In three of 11 (27%) patients with de novo AML, a lower than normal limit DI was found both in immature and mature bone marrow cells. Patients with MDS-AML had those of DI values similar to normal controls. In consequence, a significantly reduced mean DI was found in patients with de novo AML in blasts/promyelocytes (P < 0.01), and monocytes (P < 0.05) compared to both normal controls and MDS-AML. Together with data published separately, suggesting differences in granulocyte morphology, clonality, and HLA-DR expression, these data suggest biological differences between the two diseases.
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PMID:Comparison of acute myeloid leukemia occurring de novo or preceded by a myelodysplastic stage: differences in cellular DNA content. 843 3

In 1991, 4,961 bone marrow transplants (BMT) were performed in Europe by 171 teams in 21 countries. 217 were from an unrelated donor. Two years ago, this number was 99, five years ago less than ten. Main indications for unrelated BMT were CML (115), AML (32), ALL (24), SAA (19), MDS (10). Major differences exist in the European countries with regard to the number of BMT performed per number of inhabitants and with regard to indications. The present study documents the marked increased in the use of unrelated BMT in Europe. It illustrates the need for health care strategies and for clearer definitions of indications.
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PMID:Frequency and indication of unrelated bone marrow transplants in Europe. European Group of Bone Marrow Transplantation (EBMT). 844 51


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