Relation between mutations in the 5' UTR of ANKRD26 gene and inherited thrombocytopenia with predisposition to myeloid malignancies. An Egyptian study.

Inherited thrombocytopenias are a heterogeneous group of diseases characterized by a reduced number of platelets and a bleeding tendency that ranges from very mild to life threatening especially in surgery. Mutations in the 5' untranslated region (UTR) of Ankirin repeat domain 26 (ANKRD26) are responsible for autosomal-dominant form of thrombocytopenia, that is known as ANKRD26-related thrombocytopenia (ANKRD26 RT), characterized by a moderate thrombocytopenia with mild propensity to bleeding and predisposition to hematological malignancies including AML and MDS. We included 90 unrelated patients with inherited thrombocytopenia. In addition, we investigated 45 patients with ITP. Peripheral blood and bone marrow samples were collected and examined and molecular detection of mutations in the 5︡ UTR of ANKRD26 gene was performed for all the patients. Also, screening of the mutation and development of myeloid malignancies in the extended series of the affected subjects was done. ANKRD26 mutations were identified in 10% of the patients with inherited thrombocytopenia. The most common types were c.128 G > A and c.127A>T, while no mutations were found in the ITP group. In those affected, the median number of platelets was 69 x109/L (43-106) with normal MPV in most of the patients (9.4-11.6). There was a statistically significant increase in the unexpected high frequency of myeloid malignancies in the extended series of the mutated subjects compared with the ITP group-extended series (P < .001). So, we can conclude that ANKRD26 RT is associated with increased risk for developing myeloid malignancies and ANKRD26 mutations can represent a valuable tool for making therapeutic decisions.

Initial absolute monocyte count as an immune biomarker for clinical response in acute myeloid leukemia with monocytic differentiation.

BACKGROUND: Absolute monocyte count (AMC) correlates with survival outcomes in various hematologic malignancies. However, its role in myeloid malignancies including AML needs to be highlighted. So, this prospective cohort study aimed to assess the effect of AMC on the treatment outcome and survival in a 56 adult de novo AML patients with monocytic differentiation, admitted to the Clinical Hematology Unit, Internal Medicine Department, in a tertiary referral hospital in Egypt, from July 2016 to June 2019. RESULTS: The initial AMC was measured either by manual differential or the hematology automatic analyzer Sysmex XN-2000 and patients were classified by using receiver operating characteristic curve into two groups monocytopenic (≤ 4 × 109/L) and non-monocytopenic (> 4 × 109/L) group; including 24 (42.9%) and 32 (57.1%) patients, respectively. After a median follow up period of 7.7 (range 0.5-33.2) months, the monocytopenic group was associated with a significantly higher CR rate (P = 0.019), with a lower death as well as relapse and early relapse rates (P = 0.011, 0.033, and 0.002, respectively). Moreover, low initial AMC along with intensive induction were independently associated with complete response to induction chemotherapy with HR, 5.04 [1.37-18.58], P = 0.015, and 5.67 [1.48-21.71], P = 0.011, respectively by using the multivariate logistic regression model. Regarding survival, the monocytopenic group was associated with a better 3-year disease-free survival rate (P = 0.011) in univariate Cox regression only but did not reach significance in the multivariate model and did not affect the overall survival as well. CONCLUSION: Initial AMC was found to be an independent prognostic immune biomarker for treatment response in AML patients with monocytic differentiation. However, it did not appear as an independent predictor of survival in a multivariate analysis.