Inactivation of the retinoblastoma gene in acute myelogenous leukaemia.
To investigate the role of retinoblastoma susceptibility (RB) gene inactivation in leukaemogenesis, we evaluated 36 bone marrow specimens of acute leukaemia for RB protein expression by immunoprecipitation and Western blot analysis. 15 patients had no detectable RB protein at initial screening. However, nine of them were subsequently excluded due to evidence of protein degradation. Of 27 valid cases, six (22%) were repeatedly shown to lack expression of the RB protein with three different anti-RB antibodies. Five were patients with acute myelogenous leukaemia (AML) and one, mixed-lineage acute leukaemia. The RB inactivation was noted more frequently in AML (5/18, 28%) than in acute lymphoid leukaemia (0/7, 0%). By karyotyping, none of these six patients exhibited cytogenetic changes involving chromosome 13q14, the RB locus. There is no correlation between inactivation of the RB gene and FAB subtypes or cytogenetic changes. Four patients achieved complete remission with standard chemotherapy for 6, 12, 20 and 26+ months, respectively. Southern and Northern blot analyses further indicated that the RB genes were grossly intact and the level of RB transcripts did not decrease in the majority of these six patients. These results suggest that the absence of RB products in some of acute leukaemia might be regulated at the post-transcriptional level, and it imposes no significant effect on treatment response and prognosis.
Tang
J L
JL
Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, R.O.C.
Yeh
S H
SH
Chen
P J
PJ
Lin
M T
MT
Tien
H F
HF
Chen
Y C
YC
D000293:Adolescent; D000328:Adult; D000368:Aged; D004198:Disease Susceptibility; D005260:Female; D015870:Gene Expression / Q000235:genetics; D016161:Genes, Retinoblastoma / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D012175:Retinoblastoma / Q000235:genetics*
D012333:RNA, Messenger