PML/RAR alpha fusion gene is expressed in both granuloid/macrophage and erythroid colonies in acute promyelocytic leukaemia.
Acute promyelocytic leukaemia (APL) associated with a t(15;17) translocation generates a PML/RAR alpha chimaeric gene which is transcribed as a fusion PML/RAR alpha mRNA. To clarify the pathophysiologic role of PML/RAR alpha in APL patients, we examined the expression of PML/RAR alpha in haemopoietic colonies in five patients with APL by reverse transcriptase polymerase chain reaction (RT-PCR) analysis. By the two-step RT-PCR method, we demonstrated that PML/RAR alpha positive clones were present in progenitor cells including both CFU-GM and BFU-E in two cases. This result suggests that the translocation of PML/RAR alpha occurred in a pluripotent stem cell in some APL patients. In four patients we detected two amplified cDNA fragments of 780 and 640 bp which presumably arose by alternative splicing of the PML gene. Interestingly, of CFU-GM and BFU-E colonies examined in four patients, there were three different types of colonies: those expressing only the 780 bp fragment, those expressing only the 640 bp fragment, and those expressing both fragments. This suggests that alternative splicing was clonally determined in each colony. We describe a useful RT-PCR technique for the study of gene expression in a limited number of haemopoietic precursor cells.
Takatsuki
H
H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Sadamura
S
S
Umemura
T
T
Abe
Y
Y
Goto
T
T
Yufu
Y
Y
Katsuno
M
M
Hirata
J
J
Nishimura
J
J
Nawata
H
H
D000328:Adult; D000368:Aged; D001483:Base Sequence; D003001:Cloning, Molecular; D004273:DNA, Neoplasm / Q000737:chemistry; D005260:Female; D015870:Gene Expression; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000502:physiology; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D000071156:Promyelocytic Leukemia Protein; D055503:Protein Multimerization; D012333:RNA, Messenger / Q000032:analysis*; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology; D025521:Tumor Suppressor Proteins
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human