title: HRX gene rearrangement in secondary acute lymphoblastic leukemia.
abstract: The human tri-thorax gene (HRX) also called ALL-1 (Acute Lymphocytic Leukemia-1) as well as MLL (Myeloid-lymphoid or Mixed-lineage Leukemia) gene, is disrupted in the majority of leukemias with chromosomal abnormalities involving 11q23. The alteration of the gene is related to leukemogenesis of various types such as acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and acute mixed lineage leukemia. The gene is also rearranged in cases of secondary AML developing after exposure to chemotherapeutic agents, especially topoisomerase II inhibitors. In at least one report, genomic analysis of this recombination site showed the breakpoint to be a topoisomerase II binding site and that exposure to the inhibitor could induce the rearrangement. If exposure induces the rearrangement of the gene, secondary ALL as well as secondary AML could occur after exposure to these agents, because the type of leukemias with rearranged HRX gene is not limited to AML. We present here such a case of secondary ALL with this gene rearrangement which occurred during adjuvant chemotherapy for breast cancer. Although less cases of secondary ALL are reported in comparison with those of secondary AML, such case reports have been accumulating. The incidence of this type of leukemia should be clarified in the future.
authors.affiliation: Department of Hematology/Oncology, University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Ozawa
authors.forename: S
authors.initials: S
authors.lastname: Asano
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects; D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000009:adverse effects; D005260:Female; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009190:Myelodysplastic Syndromes / Q000235:genetics; D051788:Myeloid-Lymphoid Leukemia Protein; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D011519:Proto-Oncogenes; D059005:Topoisomerase II Inhibitors; D014157:Transcription Factors; D014178:Translocation, Genetic; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; C497422:KMT2A protein, human; D009687:Nuclear Proteins; D059005:Topoisomerase II Inhibitors; D014157:Transcription Factors; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; D004250:DNA Topoisomerases, Type II