title: Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Is Separated into Two Subgroups Associated with Survival by BCR-ABL Fluorescence in situ Hybridization of Segmented Cell Nuclei: Report from a Single Institution.
abstract: Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) may include the lymphoid blast crisis of chronic myeloid leukemia (CML-BC). We applied fluorescence in situ hybridization (FISH) of the BCR-ABL fusion gene to peripheral blood and/or bone marrow smears to determine whether the fusion was restricted to mononuclear cell nuclei or if segmented cell nuclei representing mature neutrophils also carried the fusion (Seg-FISH). Among 20 patients with Ph+ ALL without a prior diagnosis of CML, 9 were Seg-FISH+ and 11 were Seg-FISH-. Seg-FISH+ cases were characterized by a higher rate of p210-type BCR-ABL transcripts, higher white cell and blast counts, and a higher rate of myeloid and T-lymphoid antigen expression than Seg-FISH- cases, in addition to 'major route' cytogenetic abnormalities associated with CML-BC. Eighteen patients were treated with tyrosine kinase inhibitors (TKIs) either alone or in combination with multiagent chemotherapy, and 7 underwent allogeneic hematopoietic stem cell transplantation. Progression-free and overall survivals were greater in the Seg-FISH+ group than in the Seg-FISH- group. These results suggest that the Seg-FISH+ group represents lymphoid CML-BC that occurs de novo, while the Seg-FISH- represents Ph+ ALL in the strict sense, and the two groups are associated with survival when treated with TKIs or TKI-combined therapy.
authors.affiliation: Department of Hematology, Tenri Hospital, Tenri, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kamoda
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Izumi
authors.forename: Futoshi
authors.initials: F
authors.lastname: Iioka
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nakamura
authors.forename: Chiyuki
authors.initials: C
authors.lastname: Kishimori
authors.forename: Katsuyo
authors.initials: K
authors.lastname: Tsuda
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Fukutsuka
authors.forename: Atsuko
authors.initials: A
authors.lastname: Okumura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hayashida
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohno
mesh_terms: D002467:Cell Nucleus; D016044:Fusion Proteins, bcr-abl / Q000097:blood; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics
chemical_list: D016044:Fusion Proteins, bcr-abl