title: Therapy-related pro-B cell acute lymphoblastic leukemia: report of two patients with MLL amplification.
abstract: Improvements in chemotherapy and medical support of patients treated with chemotherapy and radiation have led to an ever-increasing number of cancer survivors. Unfortunately, a small fraction of these patients develop secondary hematologic malignancies as a consequence of their exposure to genotoxic anti-cancer regimens. Most of these are myeloid malignancies, therapy-related acute myeloid leukemia (t-AML) or myelodysplasia (t-MDS); however, a small but growing body of literature exists, which describes therapy-related acute lymphoblastic leukemias (t-ALL). Nearly all these cases are reportedly associated with translocations involving chromosome 11q23, the site of the MLL gene. We herein report two cases of ALL occurring after chemotherapy for other malignancies that showed complex karyotypic abnormalities and distinct MLL amplification by fluorescence in situ hybridization analysis. Immunophenotypic analysis showed that both cases expressed a pro-B cell (CD10-) phenotype with aberrant myeloid antigen expression. Although MLL amplification has been reported in therapy-related myeloid disease, to our knowledge this is the first report of MLL amplification occurring in therapy-related B cell ALL.
authors.affiliation: Comprehensive Cancer Center, Department of Pathology, Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Racke
authors.forename: Carol
authors.initials: C
authors.lastname: Cole
authors.forename: Alison
authors.initials: A
authors.lastname: Walker
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Jones
authors.forename: Nyla A
authors.initials: NA
authors.lastname: Heerema
mesh_terms: D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions; D005784:Gene Amplification / Q000235:genetics*; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000139:chemically induced* / Q000235:genetics*; D054448:Precursor Cells, B-Lymphoid / Q000473:pathology*; D013194:Staining and Labeling
chemical_list: D051788:Myeloid-Lymphoid Leukemia Protein