The Putative Role of Natural Killer Cells in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma.

BACKGROUND: Natural Killer (NK) cells have crucial roles in immune responses against malignant transformation including hepatocellular carcinoma (HCC). The NKG2D receptor has a critical role in the NK recognition of target cells. AIM: We assessed NKG2D receptor expression as a diagnostic biomarker for HCC detection and progression in Egyptian patients with hepatitis C virus (HCV)-related HCC. METHODS: We classified 81 patients into three groups: chronic hepatitis (21), cirrhotic (30) and HCC (30) patients, with 36 individuals enrolled to the control group. We analyzed NK levels in peripheral blood and NKG2D receptor expression in NK cells using flow cytometry. RESULTS: We observed a significant decrease in NKG2D (CD314) expression on circulating NK cells and frequency of NK cells expressing NKG2D (CD314) in HCC patients. Also, in patients, larger foci lesions significantly correlated with decreased NK cell numbers. Multiple foci numbers and patients with a Child score C significantly correlated with decreased circulating NK cells expressing NKG2D and decreased NKG2D expression. CONCLUSION: The percentage of NK cells in peripheral blood and NKG2D receptor expression could function as potential biomarkers for HCC detection and progression.

Correlation Study on HLA-DR and CD117 (c-Kit) Expressions: Its Prognosis and Treatment Response in Acute Myeloid Leukemia Patients.

INTRODUCTION: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. HLA-DR and CD117 (c-Kit) are important diagnostic markers of AML. Our objective is to determine the prognostic significance of HLA-DR and CD117 expressions in newly diagnosed AML patients and determine the correlation between HLA-DR and CD117 expressions and other prognostic markers such as cytogenetic abnormalities, FLT3-ITD, response to treatment, and patient's survival. METHODS: This study included 100 newly diagnosed AML patients. All patients were subjected to clinical, morphological, cytochemical, cytogenetic analysis, molecular genetic analysis to detect FLT3-ITD, and Flowcytometric detection of HLA-DR, CD117, and CD 34. RESULTS: The results showed that HLA-DR expression was found in 75 patients (77.3%), while CD117 expression was found in 63 patients (64.9%). Patients with HLA-DR expression showed significantly higher mean Hb concentration, significantly higher platelet count, associated with AML-FAB subtypes (M0, M1, and M2), CD34 expression, and favorable cytogenetic group. M3 subtype was significantly associated with HLA-DR-ve. While patients with CD117 expression showed significantly lower platelets count. Double positive patients (HLA-DR+ve/CD117+ve) showed significant association with the intermediate cytogenetic group, while double-negative patients (HLA-DR-ve/CD117-ve) were associated with the favorable and intermediate cytogenetic group and either positive (HLA-DR+ve /CD117-ve or HLA-DR-ve/CD117+ve) associated with poor cytogenetic groups. FLT3-ITD expression had significantly worse overall survival. CONCLUSION: The current study suggested that the expression of CD117 and HLA-DR may be a prognostic marker in AML, as they are associated with M0, M1, and M2 FAB subtypes; moreover, patients with combined HLA-DR and CD117 positive expression are associated with CD34 expression and intermediate cytogenetic group.

Patched homolog 1 (PTCHI) gene mutations can predict the outcome of chronic myeloid leukemia patients?

BACKGROUND: The Hedgehog (Hh) pathway is stimulated by inactivating mutations of Patched Homolog 1 (PTCH1) gene. There is accumulating evidence that Hh signaling plays a critical role in the pathogenesis of various haemopoietic malignancies. Particular interest has focused on the role of Hh signaling in chronic myeloid leukemia (CML). The Hh signaling is increased in BCR-ABL+ve progenitor cells and Hh signaling is further up regulated with disease progression. AIM: The aim of this study was to determine the frequency and types of PTCH1 gene mutations in Chronic Myeloid Leukemia (CML) patients and to correlate the effect of these mutations on the prognosis and outcome of CML and for predicting the imatinib response in CML patients. SUBJECTS AND METHODS: The study included fifty newly diagnosed CML patients and ten healthy volunteers (the control group) to verify the presence or absence of PTCH1 gene mutation. The patients were subjected to clinical examination, routine laboratory investigations, bone marrow examination, Cytogenetic evaluations of t(9;22) and molecular study of BCR-ABL fusion gene. All participants in this study were subjected to the assessment for the presence of PTCH1 gene mutation by DNA extraction followed by polymerase chain reaction (PCR) of genomic DNA corresponding to exon 23 of PTCH1 gene, purification of amplified PCR product, followed by sequencing analysis for detection of PTCH1 gene exon 23 mutations and the types of these mutations. RESULTS: Four types of mutations of PTCH1 gene were detected in 24 CML patients (48%), three types of them were missence while the fourth type was frame shift mutation. There was no significant association between PTCH1 gene mutation and percent of BCR-ABL fusion genes at level less than 10% at 3 months of treatment, complete cytogenetic response (CCyR) at one year, disease free survival and overall survival. However there was significant association between PTCH1 gene mutation and imatinib failure (P=0.03). CONCLUSION: PTCH1 gene mutation should be considered a promising molecular marker for predicting the probability of imatinib response in CML patients. Hedgehog pathway activation in CML patients can raise a possibility that combinations of ABL and Hh inhibitors might offer a new treatment strategy in CML and might help to effectively cure this disease.