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 the clonal chromosome abnormalities of five patients with Fanconi anemia (FA). In one with myelodysplastic syndrome (MDS), an abnormal clone was present in the bone marrow (BM): 47,XY,trp(1)(q32q44), + mar. Two had acute myeloblastic leukemia (AML), one with monosomy 7 and the other with 46,XY,add(1)(p34),del(7)(p13). In the two others without signs of MDS or AML, pseudodiploidy with 46,XX,-5, +8 and 46,XX, +5, -21 were present, respectively. The significance of these abnormalities is discussed.
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PMID:Chromosome abnormalities in bone marrow of Fanconi anemia patients. 843 15

Cytogenetic and clinical details are presented for 66 patients with myeloid malignancy and chromosome abnormalities of 3q21 and/or 3q26 (3qabns). Bone marrow and/or peripheral blood morphology was assessed for 52 cases. 3qabns in Philadelphia negative (Ph-ve) and positive (Ph+ve) cases were inv(3)(q21q26), (21 Ph-ve, 6 Ph+ve); t(3;3)(q21;q26) (nine Ph-ve, four Ph+ve); and t(3;21)(q26;q22) (four Ph-ve, six Ph+ve). Ph-ve cases also had t(1;3)(p36;q21) (three cases), and t(3;5)(q21;q31)/(q21;q35)/(q26;q21) (five cases aged < 40 years). Three cases, aged < 30 years, had t(3;12)(q26;p13) which defines a new 3qabn subgroup. Monosomy 7 and/or 5q- accompanied inv(3) or t(3;3) in 17/30 cases. All cases had a myeloid malignancy (predominantly AML M1, M4 or M7), frequent trilineage myelodysplasia, and markedly abnormal megakaryopoiesis with micromegakaryocytes (< 30 microns). Thrombocytosis occurred in two cases only. Most Ph+ve cases were in myeloid blast crisis and in Ph+ve cases alone, micro-megakaryocytes were uniquely small (10 microns) in 7/11 cases. There were equal numbers of males and females. Seven secondary leukaemias were found in Ph-ve cases with inv(3), t(3;3), t(3;21), t(1;3) or del(3)(q21). Three cases with t(3;21) (one Ph+ve) were de novo AML or had de novo aplastic anaemia. Survival was rarely greater than 12 months from detection of the 3qabn.
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PMID:Abnormalities of 3q21 and 3q26 in myeloid malignancy: a United Kingdom Cancer Cytogenetic Group study. 861 55

We report a patient with a history of leukopenia who developed acute myeloid leukemia (AML) FAB M2 and was successfully treated with induction and consolidation chemotherapy. She relapsed 7 months after initial diagnosis. Peripheral blood cells at relapse showed a t(12;15)(p13;q13), which has not been previously described in de novo or relapsed AML.
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PMID:Translocation (12;15)(p13;q13) in a patient with relapsed acute myeloid leukemia. 860 47

The t(12;21)(p13;q22) is identified by routine cytogenetics in less than 0.05% of pediatric acute lymphoblastic leukemia (ALL) patients. This translocation encodes a TEL/AML-1 chimeric product comprising the helix-loop-helix domain of TEL, a member of the ETS-like family of transcription factors, fused to AML-1, the DNA-binding subunit of the AML-1/CBF beta transcription factor complex. Both TEL and AML-1 are involved in several myeloid leukemia-associated translocations with AML-1/CBF beta being altered in 20-30% of de novo acute myeloid leukemia (AML) cases. We now demonstrate that a TEL/AML1 chimeric transcript encoded by a cryptic t(12;21) is observed in 22% of pediatric ALL, making it the most common genetic lesion in these patients. Moreover, TEL/AML1 expression defined a distinct subgroup of patients characterized by an age between 1 and 10 years, B lineage immunophenotype, non-hyperdiploid DNA content and an excellent prognosis. These data demonstrate that molecular diagnostic approaches are invaluable in identifying clinically distinct subgroups, and that the AML1/CBF beta transcription complex is the most frequent target of chromosomal rearrangements in human leukemia.
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PMID:TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. 860 6

Three patients with secondary acute leukaemia after treatment with topoisomerase II inhibitor agents are described. Two patients had acute myeloid leukaemia (AML). FAB M5a, one had pro-B-acute lymphoblastic leukaemia (ALL). The interval between initiation of chemotherapy and the onset of secondary acute leukaemia was 19-20 months. 11q23 rearrangements were detected in all cases. They were due to translocations t(11;19) (q23;p13.3), t(11;16)(q23;p13) and t(4;11)(q21;q23), respectively. Fluorescence in situ hybridization (FISH) with Yeast Artificial Chromosome (YAC) probe 13HH4 spanning the ALL-1 gene on 11q23 confirmed that in each case the ALL-1 gene had been disrupted by the translocations. The study underlined the relationship between the development of secondary acute leukaemias with 11q23 rearrangement and previous chemotherapy with topisomerase II inhibitor agents. So far, however, only six adult patients with secondary ALL with t(4;11) after treatment with topoisomerase II inhibitor agents have been reported. All with t(4;11) mostly occurs in infants or young children. Our patient received epirubicin continuously for >19 months. This indicates that both myeloid and lymphoid leukaemias with involvement of the ALL-1 gene can be induced by exogenous agents, especially topoisomerase II inhibitors. Thus they may have a common biological background. This hypothesis was substantiated by means of combined immunophenotyping and FISH (FICTION). In the case of AML M5a with t(11;19), the tumour cells with ALL-1 rearrangement expressed CD34. Moreover, the pro-B-ALL with t(4;11) was CD34 positive. These findings suggest that the cell of origin of secondary AML and ALL with 11q23 rearrangement is an immature haemopoietic progenitor cell.
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PMID:Secondary acute leukaemias with 11q23 rearrangement: clinical, cytogenetic, FISH and FICTION studies. 861 34

Two cases of myeloid leukemias (acute [AML M2] and chronic [CMC]), blastic crisis, with identical t(2;3)(p13;q26) are described. These cases had some peculiarities: no significant decrease of blood thrombocyte count in the AML patient and high increase of blood thrombocyte count during blastic phase in the CML patient; dysplastic megakaryocytes in bone marrow and unfavorable course of the disease; and short remission (3 months) in AML and short chronic phase (8 months) in CML. Clinical and morphologic findings in patients with t(2;3)(p13;q26) resembled those in cases with 3q21q26 syndrome or with other chromosome rearrangements involving 3q21 or 3q26.
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PMID:Translocation (2;3)(p13;q26) in two cases of myeloid malignancies. Acute myeloblastic leukemia (M2) and blastic phase of chronic myeloid leukemia. 862 69

MLL is fused to ENL or ELL in acute leukemias that contain t(ll;19)(q23;p13). Although ENL and ELL localize to chromosome 19, bands p13.3 and p13.1, respectively, these breakpoints are not always readily distinguished by standard cytogenetics. We therefore used reverse transcriptase-polymerase chain reaction (RT-PCR) assays to analyze 26 cases of childhood acute leukemia containing t(11;19) to determine the frequencies of ENL and ELL involvement. All 17 cases of acute lymphoblastic leukemia (ALL) had MLL/ENL fusion transcripts. By contrast, of the 9 cases of acute myeloid leukemia (AML) analyzed, 6 had MLL/ENL fusions, 2 had MLL/ELL fusions, and 1 case had no RT-PCR-detectable MLL fusion mRNA. These data suggest that the majority of 11;19 translocations involve ENL, whereas involvement of ELL is relatively uncommon in childhood acute leukemia and may be restricted to AML.
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PMID:Molecular analysis of t(11;19) breakpoints in childhood acute leukemias. 863 52

The translocation t(10;11)(p13;q14) is a recurring chromosomal abnormality that has been observed in patients with acute lymphoblastic leukemia as well as acute myeloid leukemia. We have recently reported that the monocytic cell line U937 has a t(10;11)(p13;q14) translocation. Using a combination of positional cloning and candidate gene approach, we cloned the breakpoint and were able to show that AF10 is fused to a novel gene that we named CALM (Clathrin Assembly Lymphoid Myeloid leukemia gene) located at 11q14. AF10, a putative transcription factor, had recently been cloned as one of the fusion partners of MLL. CALM has a very high homology in its N-terminal third to the murine ap-3 gene which is one of the clathrin assembly proteins. The N-terminal region of ap-3 has been shown to bind to clathrin and to have a high-affinity binding site for phosphoinositols. The identification of the CALM/AF10 fusion gene in the widely used U937 cell line will contribute to our understanding of the malignant phenotype of this line.
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PMID:The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family. 864 84

Translocation (1;19)(q23;p13) is considered a specific chromosome aberration in acute lymphoblastic leukemia (ALL). We report a case of M5 acute nonlymphocytic leukemia (ANLL) with t(1;19). In all mitoses studied from peripheral blood (PB) cells, the pathological karyotype 51,XX,t(1;19)(q23;p13),+8, +der(19)t(1;19)(q23;p13), +3mar was detected. No rearrangement of the E2A gene was detected. We believe this case shows that cytogenetically indistinguishable aberrations may be accompanied by quite different molecular events.
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PMID:t(1;19)(q23;p13) in a case of acute monocytic leukemia. 864 42

Human permanent leukemia cell lines represent powerful research tools in a multitude of investigations. The two new continuous leukemia cell lines MUTZ-2 and MUTZ-3 were derived from the peripheral blood of patients with acute myeloid leukemia (AML) FAB M2 and AML FAB M4. MUTZ-2 and MUTZ-3 cells have morphological and immunophenotypical features of myeloid and monocytic cells, respectively. While MUTZ-2 is negative, MUTZ-3 cells express the monocytic surface marker CD14, albeit weakly. The monocytic nature of MUTZ-3 cells is underlined by the expression of the monocyte-specific esterase (MSE), myeloperoxidase (MPO) and tartrateresistant acid phosphatase (TRAP) enzymes; MUTZ-2 is negative for MSE and TRAP, but expresses MPO. For sustained cell growth, both cell lines require constitutively the addition of cytokines to the culture medium and retain an absolute dependence on conditioned medium or recombinant growth factors for proliferation and survival. Incubation with single recombinant cytokines from a broad spectrum of growth factors established that the strongest proliferation response of MUTZ-2 cells was elicited by FLT-3 ligand, granulocyte colony-stimulating factor (G-CSF), macrophage CSF (M-CSF), interferon-gamma (IFN-gamma) and stem cell factor (SCF), whereas granulocyte-macrophage CSF (GM-CSF), M-CSF, interleukin-3 (IL-3) and SCF were the most effective growth factors in inducing proliferation of MUTZ-3. Both cell lines were proliferatively responsive to several further cytokines, however, to a lesser extent. Exposure to phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or the physiological all-trans retinoic acid (ATRA) had growth-inhibitory and differentiation-inducing effects on both cell lines. Using a clonogenic cell recovery assay, both cell lines were found to be sensitive to the chemotherapeutic drugs cytosine arabinoside (Ara-C) and daunorubicin (DNR), MUTZ-2 cells being more sensitive to both Ara-C and DNR treatment than MUTZ-3 cells. Chromosomal trisomies 8 and 10 were found in MUTZ-2 cells without any additional structural abnormalities. MUTZ-3 carries the rare, but recurrent AML-associated translocation (12;22)(p13;q11-q12) reflecting the karyotype of the original tumor. The main characteristics of these cell lines remained the same during about 1 year of continuous culture as well as after freezing and thawing. In summary, we established and characterized two new leukemia cell lines with myeloid or monocytic features which are growth factor-responsive, one of them carrying a unique chromosomal translocation. These cells will be of particular value for investigating the complex cytokine network and molecular events caused by chromosomal aberrations.
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PMID:Establishment and characterization of two novel cytokine-responsive acute myeloid and monocytic leukemia cell lines, MUTZ-2 and MUTZ-3. 866 38


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