Janus Kinase 2 (JAK2) is a member of a family of four Janus Kinases, 2, and 3 and tyrosine kinase 2. Mutated JAK2 (V617F) has the ability to activate downstream signal transducer and activator of transcription (STAT)-mediated transcription in the absence of the ligand erythropoietin. The autoinhibitory activity of JAK2 is disrupted by the presence of the V617F mutation. Somatic mutation in JAK2 (V617F) gene has been reported in myeloid disorders. This study reports the prevalence of JAK2V617F using amplification refractory mutation system (ARMS)-polymerase chain reaction in 246 Egyptian patients with different myeloid disorders and studied the relationship between the JAK2V617F mutation and parameters in peripheral blood. The mutation was detected among 88 patients (35.8%) with different myeloid disorders. JAK2V617F was found among 81.4% of polycythemia vera (PV), 50% of essential thrombocythemia, 46.1% of primary myelofibrosis (PMF), 33.3% of philadelphia (Ph)-negative chronic myeloid leukemia, 33.3% of myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN), and 50% of refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) patients. Hemoglobin and white blood cells were significantly higher in the mutated group of MPN including PV, essential thrombocythemia, and PMF, whereas platelet counts were higher among the mutated PV, PMF, RARS-T, and MDS/MPN group. The identification of JAK2V617F mutations has raised the prospect of developing specific JAK2V617F inhibitors to treat mutated patients.

Background: Systemic inflammatory response syndrome (SIRS) is a systemic inflammatory response to a variety of insults. Presepsin; the soluble CD14 subtype is a novel soluble CD14 molecule that is useful for diagnosing sepsis. It plays an important role in modulating the immune response to endotoxin in vitro and vivo. The aim: Of the study was to evaluate the usefulness of presepsin as a diagnostic marker of sepsis in acute leukemia. Methods: The current study was carried out on 40 adult patients with acute myeloid leukemia after receiving chemotherapy. 10 clinically normal individuals were included in the study to measure the level of presepsin. Results: This study was conducted on 50 individuals divided into 2 groups. Group I included 40 adult AML patients who fulfilled at least two of the diagnostic criteria for SIRS and Group II were 10 healthy adult persons as a control group. In Group I there were 11 patients (27.5%) having SIRS, 8 (20%) having sepsis, 9 (22.5%) having severe sepsis and 12 (30%) having septic shock. Data indicate that presepsin level was significantly higher in patients than control P = 0.017. Our results showed that the level of presepsin has a significantly positive correlation to the degree of severity of sepsis with P value 0.0001. Using the ROC curve, we found that presepsin was more specific than CRP in detection of sepsis. Conclusion: sCD14-ST (presepsin) is a new important marker for diagnosis and prognosis of sepsis. Its level increases in the first six hours after the onset of sepsis. Our data demonstrated that the concentration of presepsin is specifically increased during sepsis and is directly proportional to the degree of sepsis. Regarding sensitivity and specificity of presepsin in the discrimination of sepsis patients from healthy controls, a high specificity but low sensitivity was reported by most of the studies.

NPM1 belongs to a new category of genes that function both as oncogenes and tumor suppressor genes, depending on gene dosage, expression levels, interacting partners, and compartmentalization. Nucleophosmin mutations within exon 12 have been described as the most frequent acquired molecular abnormalities in adult and pediatric acute myeloid leukaemia (AML), mutation can be observed in nearly half of patients with a normal karyotype and is associated with a favorable outcome. NPM1 mutations are characterized by the aberrant cytoplasmic localization of NPM, the absence of CD34, involvement of several cell lineages myeloid, monocytic, erythroid and megakaryocytic but not lymphoid and a high frequency of FLT3-ITD mutation. We aimed to study the prevalence, association with Flt3 mutations, and prognostic impact of NPM1 exon-12 mutations in 71 AML patients with normal karyotype. We studied NPM1 and FLT3 by RT PCR. NPM1 gene mutation was detected among 34 patients (47.9%) and was associated with a high white blood cell count, involvement of the monocytic lineage, CD34 negativity, and high frequency of FLT3ITD. DFS and OS did not differ between mutated and unmutated NPM patients. Prospective studies are needed to confirm the definitive place of NPM mutation among patients with normal karyotype.

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BackgroundAcute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by a clonal expansion of myeloid blasts. Treatment strategies of patients with AML are based on various prognostic factors, including age and performance status of the patient, as well as cytogenetic and molecular characteristics of the leukemic clone.Our aim was to study the expression of cluster of differentiation (CD)25 in adult Egyptian patients with newly diagnosed AML and to assess its prognostic relevance.MethodsThis study was conducted on 50 newly diagnosed AML patients at the Hematology Unit, Internal Medicine Department, Alexandria Main University Hospital. All patients were subjected to full history taking, thorough clinical examination, and laboratory investigations, including detection of CD25 expression on blast cells by flow cytometry. Conventional karyotyping was done on 11 patients at the time of diagnosis.ResultsIn our study group, 12 patients were positive for CD25 expression, and this positivity was associated with worse overall survival and shorter leukemia-free survival. On evaluating the response to treatment among CD25-positive AML patients with normal karyotype, they had lower complete remission rates and higher relapse and death rates.ConclusionsExpression of CD25 in AML patients at presentation can be considered a poor independent prognostic factor.