title: Hematopoietic stem cell transplantation for pediatric mature B-cell acute lymphoblastic leukemia with non-L3 morphology and MLL-AF9 gene fusion: three case reports and review of the literature.
abstract: Mature B-cell acute lymphoblastic leukemia (B-ALL) is typically associated with French-American-British (FAB)-L3 morphology and MYC gene rearrangement. However, rare cases of mature B-ALL with non-L3 morphology and MLL-AF9 fusion have been reported, and such cases are characterized by a rapid and aggressive clinical course. We here report three such cases of pediatric mature B-ALL in female patients respectively aged 15 months, 4 years, and 4 months. Bone marrow smears at diagnosis showed FAB-L1 morphology in all patients. Immunophenotypically, they were positive for cluster of differentiation (CD)10, CD19, CD20 (or CD22), Human Leukocyte Antigen-DR, and surface immunoglobulin λ. No evidence of MYC rearrangement was detected in any of the cases by fluorescent in situ hybridization (FISH) analysis. However, MLL rearrangement was detected by FISH, and MLL-AF9 fusion was confirmed by reverse transcriptase-polymerase chain reaction. All patients achieved complete remission after conventional chemotherapy and subsequently underwent hematopoietic stem cell transplantation as high-risk ALL; patient 3 for infantile ALL with MLL rearrangement and the others for ALL with MLL rearrangement and hyperleukocytosis (white blood cell count at diagnosis >50 × 10(9)/L). At the latest follow-up for each case (12-98 months post-transplantation), complete remission was maintained. Moreover, we discuss the clinical, genetic, and immunophenotypic features of this rare disease.
authors.affiliation: Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan. sara5p@asahikawa-med.ac.jp.|Department of Pediatrics, Asahikawa Medical University, Midorigaoka-Higashi 2-1-1-1, Asahikawa, 078-8510, Japan. sara5p@asahikawa-med.ac.jp.
authors.forename: Takeo
authors.initials: T
authors.lastname: Sarashina
authors.affiliation: Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Iwabuchi
authors.affiliation: Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miyagawa
authors.affiliation: Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sekimizu
authors.affiliation: Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yokosuka
authors.affiliation: Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hamanoue
authors.affiliation: Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Iwasaki
authors.affiliation: Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Goto
authors.affiliation: Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Shiomi
authors.affiliation: Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Chihaya
authors.initials: C
authors.lastname: Imai
authors.affiliation: Division of Hemato-Oncology/Regenerative Medicine, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Goto
mesh_terms: D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D015448:Leukemia, B-Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction / Q000379:methods; D014178:Translocation, Genetic
chemical_list: C474558:MLL-AF9 fusion protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein
keywords: MLL-AF9; Mature B-ALL; Non-L3 morphology; Stem cell transplantation