[Acute monocytic leukemia after orthotopic liver transplantation: clinical features, molecular genetics, and significance thereof].
OBJECTIVE
To study the clinical features and molecular genetics of acute monocytic leukemia (AML) after orthotopic liver transplantation and significance thereof.


METHODS
The clinical manifestations, laboratory findings, development, diagnosis, treatment, and prognosis of the first case of AML after orthotopic liver transplantation in the world, a Chinese, male, aged 46, were observed. RT-PCR was used to analyze the mRNA expression of FLT3, Pim-1, and Hsp-70 in the bone marrow mononuclear cells (BMMCs) of the patient. Nucleotide sequence analysis was used to detect the mutation of FLT3-ITD. Flow cytometry was used to examine the protein expression of C-kit, a stem cell factor receptor, and platelet derived growth factor receptor-alpha (PDGFRalpha).


RESULTS
(1) Three months after the orthotopic liver transplantation the patient manifested symptoms and signs of anemia and thrombocytopenia. Laboratory tests found increase of white blood cells and myeloblasts with Auer's rods. Cytogenetic analysis showed a genotype of 46XY/47XY with an extra chromosome 8. Bone marrow examination revealed increased promonocytes. The diagnosis of chronic myelomonocytic leukemia was made. Five months after the liver transplantation the disease developed to AML. The patient underwent combined chemotherapy (HA or DA regimens) for 5 courses and showed a partial remission both hematologically and in bone marrow examination at first, however, became resistant to all chemotherapeutic agents. RT-PCR showed absence of wild type FLT3 allele. At last the patient died of infection. (2) A FLT3-ITD mutation of "insertion" type was identified in the BMMCs. The Pim-1 mRNA was weakly expressed and the expression of Hsp-70 mRNA was upregulated in the BMMCs. (3) The protein expression of C-kit and that of PDGFRalpha were both upregulated in the BMMCs as showed by flow cytometry.


CONCLUSIONS
Orthotopic liver transplantation may be complicated with acute leukemia heterogeneous in clinical features and hematology. Certain defects in cytogenetics/molecular genetics may attribute to unfavorable prognosis.
Zhang
Guang-sen
GS
Department of Hematology, Second Xiangya Hospital, Mid-South University, Changsha 410011, China.
Peng
Hong-ling
HL
Dai
Chong-wen
CW
Gong
Fan-jie
FJ
Xu
Yun-xiao
YX
Xiao
Le
L
Pei
Min-fei
MF
Shen
Jian-kei
JK
Yang
Jun-jie
JJ