A granulocytic population with rearranged immunogenotype in chronic myelocytic leukemia blast crisis and Philadelphia-chromosome-positive acute leukemia with cross-lineage nature.
Two patients with chronic myelocytic leukemia (CML) mixed crisis and one with Philadelphia-chromosome-positive (Ph1 +) acute lymphoblastic leukemia (ALL) with cross-lineage nature had a considerable number of granulocytes with monoclonally rearranged immunogenotype. The gene configurations of immunoglobulin heavy chain (IgH), T-cell receptor beta chain (TCR beta), and gamma chain (TCR gamma) in the granulocytic cells were identical to those in the blasts, indicating that both the blasts and the granulocytes were derived from common leukemic progenitors with the IgH gene rearrangements. In a colony assay of cells from in the Ph1 + ALL patient, the leukemic cells showed the potential to differentiate into granulocytes in the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte-CSF (G-CSF). Interleukin 7 (IL-7) exerted synergistic effects on colony and cluster formation in cultures with these cytokines. Further, IL-3, GM-CSF, and G-CSF receptor gene expression was found in the leukemic cells. Our findings indicate that the Ph1 + common progenitors in these three patients preserved the potential for granulocytic differentiation even after the occurrence of the Ig (and TCR) gene rearrangements as the first genomic event in lymphocyte differentiation. The phenomenon of cross-lineage in leukemic cells, at least in Ph1 + leukemia, can be considered to demonstrate the potential of leukemic progenitors to differentiate in multiple directions.
Kita
K
K
Second Department of Internal Medicine, Mie University School of Medicine, Tsu, Japan.
Shimizu
N
N
Miwa
H
H
Ikeda
T
T
Nishii
K
K
Morita
N
N
Uchida
T
T
Shirakawa
S
S
Tsutani
H
H
Nasu
K
K
D001483:Base Sequence; D001752:Blast Crisis / Q000235:genetics*; D015139:Blotting, Southern; D002454:Cell Differentiation; D003114:Colony-Forming Units Assay; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D005838:Genotype; D006098:Granulocytes; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology*; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D010677:Philadelphia Chromosome; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology*