[PRAME mRNA expression in newly diagnosed acute myeloid leukemia patients and its application to monitoring minimal residual disease].
OBJECTIVE
To investigate the expression level of preferentially expressed antigen of melanoma (PRAME) mRNA in newly diagnosed acute myeloid leukemia (AML) patients and evaluate its usefulness for detecting minimal residual disease (MRD).


METHODS
PRAME mRNA levels were detected in bone marrow samples from 142 newly diagnosed AML patients (72 of them didn't express any specific fusion gene) by TaqMan based real-time quantitative PCR methods, and were serially monitored in 60 bone marrow samples from 9 follow-up patients (2 of them without specific fusion gene), including 3 in continuous complete remission, 6 in hematological relapse. Bone marrow samples from 22 bone marrow donors (NBM) were served as normal controls. Samples from 7 AML1-ETO (+) M2 patients were detected for AML1-ETO mRNA simultaneously. abl was selected as control gene, PRAME and AML1-ETO mRNA levels were expressed by their copies/abl copies in percentage.


RESULTS
All NBM samples expressed PRAME mRNA and the upper limit was 0.28%. For all newly diagnosed AML patients, median PRAME mRNA level was 3.97% (0.00%-714.97%), 76.8% of them was higher than 0.28%, 54.9% had over 1-log increasing and 26.1% had over 2-log increasing. For patients without specific fusion gene, median PRAME mRNA level was 0.60% (0.00%-408.72%), 56.3% of them was over 0.28%, 32.4% and 11.3% had over 1-log and 2-log increasing, respectively. There was a significant difference in PRAME mRNA levels between subtypes of AML patients (P<0.01). AML1-ETO (+) M2 patients expressed the highest levels (all P<0.01), followed by acute promyelocytic leukemia patients with S type PML-RAR alpha fusion gene. PRAME and AML1-ETO mRNA levels of follow up patients displayed similar kinetic patterns, and correlated well in 43 follow up samples (r=0.88, P<0.01). PRAME mRNA levels in 3 hematological relapsed patients increased above 0.28% 1-4 months ahead relapse, and in other 3 relapsed patients the levels never decreased to normal range even in remission.


CONCLUSIONS
PRAME mRNA could be used to monitor MRD for AML patients with higher than normal levels, and it increases over or persistently higher than normal range predicts hematological relapse.
Qin
Ya-zhen
YZ
Institute of Hematology, People's Hospital of Peking University, Beijing 100044, China.
Li
Jin-lan
JL
Zhu
Hong-hu
HH
Li
Ling-di
LD
Chang
Yan
Y
Hao
Le
L
Wang
Ya-zhe
YZ
Jiang
Bin
B
Lu
Xi-jing
XJ
Liu
Yan-rong
YR
Huang
Xiao-jun
XJ
Chen
Shan-shan
SS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D000951:Antigens, Neoplasm; C404944:PRAME protein, human; D012333:RNA, Messenger