Molecular and phenotypic analysis of Philadelphia chromosome-positive bilineage leukemia: possibility of a lineage switch from T-lymphoid leukemic progenitor to myeloid cells.
The occurrence of acute bilineage leukemia is thought to be the malignant transformation of a myeloid or lymphoid leukemic progenitor with the potential to differentiate into the other lineages; however, the mechanisms of this lineage switch are not well understood. Here, we report on the extremely rare case of adult Philadelphia chromosome-positive acute bilineage leukemia, which is characterized by T-cell acute lymphoblastic leukemia and acute myelomonocytic leukemia. Chromosome analysis showed 46,XY,del(7)(p11.2),t(9;22)(q34;q11.2) in all metaphases and a minor BCR/ABL chimeric gene was detected in these leukemic cells by PT-PCR. When the CD5+ and CD5- cells were sorted, a fusion gene of BCR/ABL and the same clonally rearranged band of a T-cell receptor (TCR) gene were detected in both populations. Nucleotide sequencing of the TCR-gamma gene revealed the clonal rearrangement of the V8-JGT2 complex in both populations. Overexpression of PU.1, which plays a fundamental role in myelomonocyte development, was found in the sorted CD34+CD7+ and CD5-, but not CD5+ cells. These results suggest that leukemic progenitor cells in the T-lineage with the del(7) and t(9;22) have the potential to differentiate into myeloid lineage, and that enforced PU.1 expression may contribute in part of this phenomenon.
Monma
Fumihiko
F
Division of Hematology and Oncology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Nishii
Kazuhiro
K
Ezuki
Shiho
S
Miyazaki
Toshiyasu
T
Yamamori
Shunji
S
Usui
Eiji
E
Sugimoto
Yuka
Y
Lorenzo V
Felipe
F
Katayama
Naoyuki
N
Shiku
Hiroshi
H
D019070:Cell Lineage; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D023461:Myeloid Progenitor Cells / Q000473:pathology; D010677:Philadelphia Chromosome; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D014178:Translocation, Genetic; D017211:Treatment Failure
D016692:Receptors, Antigen, T-Cell, gamma-delta; D016044:Fusion Proteins, bcr-abl