Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present two cases in which translocations involving 21q22 were found at presentation in acute nonlymphocytic leukemia (ANLL). The first of these translocations, t(3;21)(q26-q27;q22), is previously unknown in ANLL, but appears indistinguishable from that reportedly associated with Philadelphia-positive chronic myelogenous leukemia. The second case involves t(15;21)(q21-q22;q22), a translocation previously undescribed in ANLL. Both of these exchanges involve 21q22 plus another chromosome region associated with leukemogenesis. We attempted to interrelate these cytogenetic data with the oncogenic significance of 21q22.
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PMID:Novel translocations in acute nonlymphocytic leukemia. Two cases involving chromosome 21, band q22. 229 84

Cellular or proto-oncogenes are normal cellular genes important in normal cell growth and development. In some instances abnormal expression of these genes is associated with altered cell growth or with malignant transformation. Abnormalities of cellular oncogenes are common in human leukemias. These arise by multiple mechanisms such as mutation, translocation, amplification, and others. Sometimes more than one abnormality is present within a single oncogene. In other instances, a leukemia cell may contain abnormalities of several different oncogenes. Some oncogene abnormalities are relatively specific for certain leukemias and occur in almost all cases; examples include ABL in chronic myelogenous leukemia or MYC in Burkitt leukemia/lymphoma. Other abnormalities are also relatively specific but occur in only some cases such as NRAS in acute myelogenous leukemia or BCL2 in B-cell acute lymphoblastic leukemia. In other leukemias, such as most cases of acute lymphoblastic leukemia and chronic lymphocytic leukemia, oncogene abnormalities are uncommon. The precise role of oncogenes in the pathogenesis of human leukemia is unknown. Retrovirus transduced versions of some of the oncogenes modified in human leukemias cause leukemia in animals. Other oncogenes, modified or unmodified, transform animal and human hematopoietic cells in vitro. Some oncogene products are hematopoietic growth factors or growth factor receptors while others regulate cell proliferation or differentiation by diverse mechanisms. Disruption of the balance between these processes seems the most likely mechanism of oncogene related leukemogenesis. If the role of oncogenes in human leukemias can be defined, innovative diagnostic and therapeutic strategies may be forthcoming.
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PMID:Oncogenes and leukemia. 240 17

The incidence of acute myeloid leukemia (AML) in CBA/H mice following exposure to single acute doses of ionizing radiation has previously been determined. A high proportion of these AMLs are characterized by rearrangement of murine chromosome 2 in the C2 and/or E5-F regions, and there is evidence that these events are a direct consequence of radiation damage to multipotential hemopoietic cells. Using a combination of in situ chromosome hybridization and mRNA analyses, we show that the cytokine gene interleukin-1 beta (IL-1 beta) is encoded in the chromosome 2 F region and is translocated in a chromosome 2---2 rearrangement in an x-ray-induced AML (N36). Also, IL-1 beta is specifically deregulated in N36 and in two other chromosome 2-rearranged AMLs but not in a fourth, which has two cytogenetically normal chromosome 2 copies. We suggest that radiation-induced specific chromosome 2 rearrangement associated with IL-1 beta deregulation may initiate murine leukemogenesis through the uncoupling of normal proliferative control mechanisms in multipotential hemopoietic cells.
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PMID:Interleukin-1 beta gene deregulation associated with chromosomal rearrangement: a candidate initiating event for murine radiation-myeloid leukemogenesis? 257 38

Certain hematopoietic disorders and immunodeficiency states are known to carry a risk of developing acute nonlymphocytic leukemia. In the past some of them have been classified by a variety of terms ranging from refractory anemia to preleukemia, but are currently grouped into a new concept of the myelodysplastic syndromes (MDS). The purpose of this article is to briefly review the updated knowledge of the MDS with emphasis on the clonal origin, natural history and mechanisms of leukemogenesis.
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PMID:[Preleukemic disorders]. 264 30

While activation of the protooncogene c-N-ras is observed regularly in acute myelogenous leukemia, amplification of c-myc in AML cells or derived lines is uncommon. In particular, concurrent ras/myc activation, which has been shown to be critical in several elegant models of malignancy, has been demonstrated in a very small number of human tumors or derivative cell lines. A cell line, RED-3, is described which was derived from cells of a patient with aggressive acute leukemia which exhibits many markers of lineage infidelity. DNA from this cell line contains an activating point mutation of c-N-ras as well as 20-30-fold amplification of c-myc. After HL-60, this is the second example of ras/myc activation in AML derived cells and demonstrates that this lesion is not unique to HL-60. Rather, it may be important in leukemogenesis in a small proportion of AML patients.
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PMID:c-myc amplification coexistent with activating N-ras point mutation in the biphenotypic leukemic cell line RED-3. 265 2

We have screened a large series of primary human leukemias for activating point mutations at codons 12, 13 and 61 of the N-ras and K-ras proto-oncogenes and at codons 12 and 61 of the H-ras proto-oncogene by using panels of oligonucleotide probes in conjunction with polymerase chain reaction gene amplification. 13 of 64 (20%) acute lymphoblastic leukemia cases had ras gene mutations mostly involving N-ras codon 12/13, G-A (gly-asp) transitions. Consistent with previous studies, a comparable pattern and frequency of ras mutation was found amongst 45 cases of acute myeloid leukemia and myelodysplasia. By contrast, of 30 cases of mature B cell chronic lymphocytic leukemia, only one in terminal prolymphocytoid transformation harboured an activated ras gene. These patterns of mutation did not correlate with ras gene methylation state, a finding not obviously compatible with differential gene accessibility being an important determinant of ras gene mutation patterns in leukemogenesis. Our data suggest that activated ras is more important in tumourigenesis of immature than mature lymphocyte progenitors whilst similar mechanisms associated with aetiology and/or target cell susceptibility probably underlie the similar patterns of ras gene mutations seen in acute leukemias of both myeloid and lymphoid cell lineages.
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PMID:Analysis of ras gene mutations and methylation state in human leukemias. 266 44

A case of acute myelocytic leukemia (AML-M2) with a late appearance of Philadelphia chromosome (Ph1) is presented. Chromosome analysis revealed a normal karyotype at the time of diagnosis and for 23 months, when hematological relapse occurred, accompanied by abnormal clones, 46, XX, t(9;22) (q34;q11) (78%) and 45,XX, -16, t(9;22) (q34;q11), del (5) (q13q31) (22%). The patient died of GVHD after bone marrow transplantation. Molecular analysis confirmed bcr gene rearrangement in the cells with Ph1 chromosome. Acquisition of Ph1 chromosome during the course of hematological malignancies other than CML is extremely rare. This case is undoubtedly important for the understanding of leukemogenesis and the evolution of leukemia clones. The authors discussed possible mechanisms of Ph1 acquisition in the late stages of AML.
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PMID:[Late appearance of Philadelphia chromosome with bcr gene rearrangement in an acute myelocytic leukemia patient]. 269 64

Leukemic blast cells are thought to arise from clonal expansion of a single transformed hematopoietic cell. This generality is supported by the rarity of convincing reports on acute myeloblastic leukemia (AML) with two karyotypically independent clones. Relying on sequential cytogenetic analyses, we identified such clones in two children with relapsed AML. The first case, classified as M2 leukemia in the French-American-British (FAB) classification system, had a t(8;21) (q22;q22) at diagnosis; 16 months later, at relapse, the leukemic cells had uniform morphologic features similar to those observed at diagnosis, except that two independent clones were present: one with the original t(8;21) and the other with t(11;22)(q23;q13) [corrected]). The second case was initially classified as FAB M1 leukemia with a t(8;21) (q22;q22). At relapse, 16 months later, the blast cells appeared morphologically uniform and similar to the diagnostic specimen; however, in addition to the original t(8;21) clone, there was a t(1;11) (p32;q23) [corrected]. These findings suggest that separate leukemogenic events affecting different progenitor cells can occur in rare cases of AML. The presence of two karyotypically independent clones could also be explained by multistep leukemogenesis; that is, more than one cell from a common pool of preleukemic cells could be affected by the transforming event, resulting in two independent clones. Alternatively, in light of recent reports of therapy-related leukemias with an 11q23 translocation, the new independent clone in these two patients could represent a therapy-related secondary malignancy. Thus, 11q23 translocations may occur preferentially in stem cells that are more susceptible to treatment-induced malignant transformation.
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PMID:Two karyotypically independent leukemic clones with the t(8;21) and 11q23 translocation in acute myeloblastic leukemia at relapse. 271 98

Five patients with acute nonlymphocytic leukemia (ANLL) with chromosomal aberrations involving bands 9q21-q22 are described. The abnormalities were an interstitial deletion in two cases of ANLL FAB type M4 and M4 with eosinophilia, a terminal deletion in two cases of M4 and M5 type ANLL, and a translocation in an M2 ANLL. A review of reported cases of ANLL with abnormalities of chromosome 9 revealed a clustering of breaks at the region 9q21-q22, suggesting a possible role for these bands in leukemogenesis.
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PMID:Involvement of bands 9q21-q22 in five cases of acute nonlymphocytic leukemia. 273 Nov 48

An amphotropic retroviral vector containing the bacterial neomycin phosphotransferase gene (neo) was used to infect blast cells from patients with acute myeloblastic leukemia. The infected cells acquired a G418-resistant phenotype that was stable as measured in a clonogenic assay and in long-term suspension culture. Thus, gene transfer into stem cells was accomplished by this procedure. This approach for manipulating gene expression in blast stem cells provides a means to assess the roles of a variety of genes in self-renewal, differentiation, and leukemogenesis.
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PMID:Introduction of new genetic material into human myeloid leukemic blast stem cells by retroviral infection. 283 45


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