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Different Genetic Pathways in Leukemogenesis for Patients Presenting With Therapy-Related Myelodysplasia and Therapy-Related Acute Myeloid Leukemia

Pedersen-Bjergaard, Jens ; Pedersen, Michael ; Roulston, Diane ; Philip, Preben

Blood, 1995-11, Vol.86 (9), p.3542-3552 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Different Genetic Pathways in Leukemogenesis for Patients Presenting With Therapy-Related Myelodysplasia and Therapy-Related Acute Myeloid Leukemia
Autor: Pedersen-Bjergaard, Jens ; Pedersen, Michael ; Roulston, Diane ; Philip, Preben
Assuntos: Acute Disease ; Adult ; Aged ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents, Alkylating - adverse effects ; Autoimmune Diseases - drug therapy ; Cell Transformation, Neoplastic - genetics ; Chromosome Aberrations ; Chromosome Deletion ; Cocarcinogenesis ; Combined Modality Therapy ; Disease Progression ; Enzyme Inhibitors - adverse effects ; Female ; Hodgkin Disease - drug therapy ; Hodgkin Disease - radiotherapy ; Humans ; Iodine Radioisotopes - adverse effects ; Leukemia, Myeloid - chemically induced ; Leukemia, Myeloid - genetics ; Male ; Middle Aged ; Myelodysplastic Syndromes - chemically induced ; Myelodysplastic Syndromes - genetics ; Neoplasms - drug therapy ; Neoplasms - radiotherapy ; Neoplasms, Second Primary - chemically induced ; Neoplasms, Second Primary - genetics ; Organoplatinum Compounds - adverse effects ; Topoisomerase II Inhibitors ; Translocation, Genetic
É parte de: Blood, 1995-11, Vol.86 (9), p.3542-3552
Descrição: Development of myelodysplasia (MDS) with subsequent progression to acute myeloid leukemia (AMD is an example of the multistep process of malignant transformation in which each step often relates to genetic abnormalities that can be directly seen as chromosomal aberrations. Therapy-related MDS and AML (t-MDS and t-AML) may serve as an ideal model for a study of the genetic evolution of MDS and AML because chromosomal abnormalities are observed in most cases and because the disease is often diagnosed early due to a close patient follow-up. The cytogenetic characteristics at diagnosis were studied in 137 consecutive cases of t-MDS and t-AML, including 22 new cases, and correlated with the clinical characteristics and the course of the disease. Balanced translocations to chromosome bands 11q23 and 21q22 represent primary steps in pathways leading directly to overt t-AML. Specific chromosomal deletions or losses, on the other hand, represent primary or secondary events in alternative pathways leading to t-MDS with potential for subsequent transformation to overt t-AML. Loss of a whole chromosome 7 (-7) or deletion of its long arm (7q-) and deletion of the long arm of a chromosome 5 (5q-) were the most frequent primary abnormalities significantly related to t-MDS. Loss of a whole chromosome 5 (-5) was also a primary event, but surprisingly, was observed equally in t-MDS and in t-AML. Deletion of chromosome 13, including bands q13q14, was another less common primary aberration of t-MDS. Except for -7 and del(13q), these primary aberrations were most often observed together with secondary abnormalities. These included balanced aberrations involving band 3q26 and various deletions of chromosome 3, a gain of a whole chromosome 8, deletions of the short arm or loss of chromosomes 12 and 17, loss of a whole chromosome 18, and deletions of the short arm of chromosome 21. Deletions or loss of chromosomes 5 and 7 were significantly associated with previous therapy with alkylating agents (P = .002), and balanced translocations to chromosome bands 3q26, 11q23, and 21q22 were significantly associated with previous therapy with drugs targeting DNA-topoisomerase II (P < .00005). Other characteristic aberrations were not related to any specific type of therapy. The molecular changes believed to contribute to the development of t-MDS and t-AML have been identified for many of these chromosomal abnormalities.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Different Genetic Pathways in Leukemogenesis for Patients Presenting With Therapy-Related Myelodysplasia and Therapy-Related Acute Myeloid Leukemia

Pedersen-Bjergaard, Jens ; Pedersen, Michael ; Roulston, Diane ; Philip, Preben

United States: Elsevier Inc

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