Abstract
Genetic alterations of the mixed-lineage leukemia (MLL) gene are commonly implicated in the development of acute leukemia. In acute myeloid leukemia (AML), a partial tandem duplication (PTD) of MLL occurs in about 5%-11% of patients, mainly in adults and rarely inchildren( Meyer C et al Leukemia 2013) .It is not known whether the initial expression level of MLL-PTD affects the prognosis of AMLs. Therefore, we analyzed the clinical data of 36 AML patients with MLL-PTD treated in our institute from January 2014 to January 2016, and tried to investigate whether the initial level of MLL-PTD has an impact on the prognosis of AML patients.
MLL-PTD is present in adult non-leukemichematopoiesisand observed in bone marrow and peripheral blood of adult healthy individuals. In order to identify the threshold of MLL-PTD for AML patients, a control group of bone marrow samples from 29 normal adult donors were tested. The median value of MLL-PTD was 0.046(0.014¡«0.080)%. Patients with AML were considered MLL-PTD positive if their expression level was higher than 0.08%.
430 patients were newly diagnosed AML and treated in institute between January 2014 and January 2016. Among these AML patients, AML patients with MLL-PTD were selected as the subject patients. The following inclusion criteria were applied: (1) more than 16 years old; (2)Bone marrow MLL-PTD/ABL£¾0.08%; (3)receivedmore than 2 cycles of chemotherapy. Our study was approved by the Ethics Committee of Peking UniversityPeople¡¯s Hospital.All patients offered signed informed consent to participate in the study.The cutoff date for follow-up was Match 31, 2016.
Of the 430 de novo AML patients, 36(8.4%) patients were MLL-PTD positive. The median age was 48(22¡«72) years. 28 cases were diagnosed M2, and the others included 4 cases of M4, 2 cases of M5 and 2 cases of M6. 5 cases were FLT3-ITD mutation+, 2 cases were NPM1 mutation+,7cases were double-CEBPA mutation+.
The complete remission (CR) rate after first induction chemotherapy was 58.3%, the total CR rate after second chemotherapy was 66.7%, 1 case achieved CR after third chemotherapy, and 1 case achieved CR withsorafenibtreatment. 2 cases receivedallo-HSCT. In the 26 cases who achieved CR1, 7 cases relapsed at a median of 5 months. The median follow-up was 4.8 (2¡«17.2) months, and 10 cases were died.
According to Hans B. Ommenetal¡äs study (Ommen HB et al Br J Haemato2014), ROC analysis was performed to determine the potential optimal MLL-PTD cutoff level to predict the incidence of CR after second induction chemotherapy. We established MLL-PTD ¡Ý1% as the cut of value. 19 cases were MLL-PTD £¼1% as the low level group and 17 cases were MLL-PTD ¡Ý1% as the high level group. Distribution of FAB type (M2 incidence 100% vs. 53%, P=0.003) and biallelic CEBPA mutation incidence (37% vs. 0%, P=0.008) were significantly different between the two groups. (Table 1) The CR rate after first induction chemotherapy (78.9% VS 35.3%, P=0.008) and CR rate after second induction chemotherapy (84.2% VS 47.1%,P=0.001) were also significantly different between the two groups.(Table 2) Logistic regression analysis showed that high level of MLL-PTD was the only independent risk factor of CR rate after second induction chemotherapy (OR=0.16, P=0.024). There were 5 patients died in each group. The 15-month estimated OS between low-level and high-level groups was not significantly different (51.5% vs .67.2%, P=0.607).
Our data indicates that the initial level of MLL-PTD in patients with AML affects clinical prognosis, and patients with high initial level MLL-PTD have a lower CR rate. Low level of MLL-PTD may not play a part in the development of acute leukemia. And it needs further observation to identify the effect of initial MLL-PTD level on survival.
Kong Jun and Jiang Hao contributed equally to this work
Disclosures
No relevant conflicts of interest to declare.
USING EXTENSIVE READING TO IMPROVE ECONOMIC VOCABULARY FOR SECOND-YEAR STUDENTS AT THE UNIVERSITY OF LANGUAGES AND INTERNATIONAL STUDIES – VIETNAM NATIONAL UNIVERSITY, HANOI
