Correlation Between Platelet Counts And Leukemia Mutations In Acute Myeloid Leukemia

Background and Objective:Acute myeloid leukemia(AML) is a hematopoietic stem cell malignant disease, with abnormal proliferation of leukemic and immature cell and injury of normal hematopoiesis. AML is also a highly heterogeneous disease with molecular and cytogenetic changes, which have an crucial effect on the differentiation and proliferation of hematopoietic lineage. Megakaryocyte, as an important partner of myeloid lineage, it usually presented with reduced or absent status in AML and these patients always experience a thrombocytopenia and bleeding tendency, however, some people present with normal or even advanced megakaryocyte counts resulting in normal platelet counts and even thrombocytosis. In the last century, AML patients with abnormalities in chromosome 3q were reported to have thrombocytosis, in the next decades, it has been demonstrated patients with DNMT3 A and NPM1 presents higher platelet counts while those with CEBPA mutation have lower platelet counts, however, pathogenesis have not been well clarified. Thus, in this study, we mainly reviewed correlation between mutation and megakaryocyte and platelet in AML and analysis the clinical characteristic and prognosis of AML patients with normal platelet counts. Furthermore, we investigate the thrombopoietin(TPO), interlectin-6(IL-6) and c-MPL levels in AML patients.Methods:1.We retrospectively reviewed three hundred and fourteen(314) de novo AML patients except acute promyelocytic leukemia(APL) who were treated in the First Affiliated Hospital of Suzhou University from 2013 January to 2015 April in this study. Among them, were 178 males and 136 females, the median age on diagnosis were 42-year-old. 180 patients cytogenetically-normal AML(CN-AML) were mainly enrolled to explore relation between mutation and platelet counts(PLTs). In particular, we analyze the clinical features and prognosis of AML patients who have normal PLTs onset of diagnosis.2. To explore the mechanism PLTs production in AML, we investigated the endogenous production of TPO, IL-6 and c-MPL expression levels in de novo AML patients.Results:1. Of all the 314 AML patients, patients with DNMT3 A mutation(n=30) and NPM1 mutation(n=46) have higher PLTs while CEBPA mutaions(n=35) have the lowest PLTs compared with those without mutations. No statistical difference were found between AML patients with FLT3-ITD(n=49), C-KIT(n=30) mutation subgroups and mutation-negative groups. To minimum the impact of abnormal cytogenetics on PLTs, we mainly focus on the analyze of the 180 CN-AML, mutations in DNMT3 A were found in 27 patients, NPM1 in 36 patients, FLT3-ITD in 32 patients, CEBPA in 26 patients,C-kit in 11 patients and no mutations were not found in 48 patients. The platelet counts(PLTs) of DNMT3A+ and NPM1+ AML patients have higher PLTs compared to those without mutation, the CEBPA+ AML have lower PLTs than those without mutation.2. AML patients with PLTs less than 30×109/L have higher CR rate(85.6%)compared with patients with PLTs over 100×109/L(65.8%), P<0.05. Patients with normal platelet counts at first diagnosis presented adverse molecular and cytogenetically markers and worse chemotherapy effect.3. De novo AML patients have higher TPO, IL-6 and c-MPL levels than normal patients and AMLs in complete remission status. We divided these AML patients with 3 groups according to PLTs: PLTs less than 30, PLTs from 30 to 100 and PLTs over than 100×109/L. De novo AML patients with PLTs over 100×109/L have higher TPO and c-MPL levels, no statistical differences of IL-6 levels were found in the three different groups in AML patients. DNMT3 A and FLT3-ITD positive AML presented an expensive TPO tendency while DNMT3 A patients showed higher c-MPL levels.Conclusion:1. Various mutations in AML pose an effect on megakaryocytes and platelet counts, particularly, patients with DNMT3 A, NPM1 mutations usually presented a higher and platelet counts while those with CEBPA mutations have lower when comparing with patients without molecular abnormalities.2. AML patients with PLTs<30 have higher complete remission rate while de novo AML patients with normal platelet counts at first diagnosis seemed to presented an unique group, they usually have adverse molecular and cytogenetically markers and poorer chemotherapy effect.3. De novo AML patients who have normal PLTs have higher TPO and C-MPL levels, DNMT3 A and FLT3-ITD positive AMLs presented an expensive TPO tendency while DNMT3 A patients showed higher C-MPL levels.