Covert preleukemia driven byMLLgene fusion
| Autor: | Claus Meyer, Ester Mejstrikova, Jan Stary, Lyndal Kearney, Katerina Muzikova, H. Ptoszková, Susan M. Colman, Rolf Marschalek, Zuzana Zemanova, Ondrej Hrusak, Sharon W. Horsley, Jan Zuna, Tatiana Burjanivova, Jan Trka, Mel Greaves |
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| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Myeloid Adolescent Preleukemia Clone (cell biology) Biology Polymorphism Single Nucleotide Fusion gene Leukemia Promyelocytic Acute Precursor B-Cell Lymphoblastic Leukemia-Lymphoma hemic and lymphatic diseases Biomarkers Tumor Genetics medicine Humans Myeloid Cells Gene Rearrangement Acute leukemia Gene Expression Regulation Leukemic Forkhead Box Protein O3 Forkhead Transcription Factors Histone-Lysine N-Methyltransferase Gene rearrangement medicine.disease Leukemia medicine.anatomical_structure Cytogenetic Analysis Immunology Neoplastic Stem Cells Cancer research Female Bone marrow Gene Fusion Chromosomes Human Pair 19 Myeloid-Lymphoid Leukemia Protein |
| Zdroj: | Genes, Chromosomes and Cancer. 48:98-107 |
| ISSN: | 1098-2264 1045-2257 |
| DOI: | 10.1002/gcc.20622 |
| Popis: | Acute leukemia is considered to be a two- or multiple-step process. Although there is a considerable knowledge regarding the character of the "first hit," the nature of the "second hit" remains unanswered in most of the cases including leukemias with MLL gene rearrangement. We demonstrate here a striking sequence of events, which include a covert, protracted preleukemic phase characterized by a dominant MLL/FOXO3A clone with intact myeloid differentiation and the subsequent acquisition of a secondary genetic abnormality, leading to overt lymphoblastic leukemia. Backtracking of the secondary acute lymphoblastic leukemia (sALL) with the MLL rearrangement showed no blasts in the bone marrow (BM) during the protracted preleukemic phase. However, at the same time (more than 1 year before the sALL diagnosis) the MLL/FOXO3A was present in up to 90% of BM cells including myeloid lineage, suggesting that the fusion arose in a multipotent progenitor. To identify potential "second hit" precipitating sALL we compared DNA in preleukemic versus fully leukemic samples. The analysis revealed a 10 Mb gain on 19q13.32 in the sALL, absent in the preleukemic specimen. These data provide insight into the dynamics of leukemogenesis in secondary leukemia with MLL rearrangement. |
| Databáze: | OpenAIRE |
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