Renin-Angiotensin System Expression in the K562 Human Erythroleukaemic Cell Line

Local renin-angiotensin system (RAS) may affect leukaemic cell production within the bone marrow microenvironment. Angiotensin-converting enzyme (ACE), renin, and angiotensin could influence leukaemogenesis. In this study, mRNA expressions of the major RAS components (ACE, renin, and angiotensinogen) in K562 human erythroleukaemia cell line have been searched by Real Time quantitative polymerase chain reaction. K562 blasts are multipotential, haematopoietic malignant cells that spontaneously differentiate into recognisable progenitors of the erythrocyte, granulocyte and monocytic series. We observed significant expressions of ACE, renin, and angiotensinogen in K562 leukaemic blast cells. Therefore, K562 human erythroleukaemia cell line may serve as an in vitro model to elucidate the role of RAS in leukaemia and to test the effects of RAS-affecting drugs on leukaemic cellular proliferation.WoSScopu

Angiotensin Converting Enzyme Insertion/Deletion Gene Polymorphisms In Leukemic Hematopoiesis

Local bone marrow renin-angiotensin system (RAS) is an autocrine-paracrine system affecting normal and neoplastic hematopoiesis. Angiotensin converting enzyme (ACE) converts angiotensinogen-I to its physiologically active peptide angiotensinII, which stimulates proliferation and differentiation of hematopoietic stem cells through angiotensin II type 1 receptors. We investigated the ACE insertion/deletion (I/D) gene polymorphisms in patients with hematological malignancies including acute and chronic leukemia, myelodysplastic syndrome and multiple myeloma. Our results showed that 80.4% of the patients represented ID/II genotype, whereas it was 55.9% of the control group and 3.2 fold increased disease risk in the existence of insertion allele (ID/II). This is the first study demonstrating possible effects of ACE I/D gene polymorphism of the local bone marrow RAS components on leukemic hematopoiesis.WoSScopu

Bone Marrow Iron Staining Is a Reliable Test For Elimination of Iron Deficiency Anemia Rather Than Its Diagnosis

Iron deficiency anemia (IDA) is the most frequent type of anemia. The use of biochemical markers is a challenging way of diagnosis in case of inflammation and functional iron deficiency. The role of bone marrow aspirate iron staining is criticized because it is an invasive method and has no accurate standardization. This study was planned to find the value of bone marrow iron staining in diagnosis of iron deficiency. Four hundred and seven cases who had bone marrow aspirate iron staining and simultaneous serum iron tests have been reviewed retrospectively and 47 such cases were evaluated prospectively. Bone marrow iron was negative in 125 (%30.7) cases in retrospective cohort. There was significant differences in serum iron, ferritin, transferrin saturation between bone marrow iron negative and positive cohorts (p<0.001). Low serum transferrin saturation (<15%) and ferritin (<15 ng/ml) levels are consistent with iron deficiency. On this standard, in both retrospective and prospective cohorts, rates for specificiy (85.5% and 90.4%, respectively) and negative predictivity (97.5% and 100%, respectively) of bone marrow iron staining were relatively high compared with the sensitivity and positive predictivity of the same test. The results of this study show that the evaluation of bone marrow iron staining is a more reliable test for the elimination of IDA rather than its diagnosis.WoSScopu

Renin-Angiotensin System (Ras) Expressions in Myeloid Leukemic Cell Lines

The aim of this study is to search critical renin-angiotensin system (RAS) elements in myeloid leukemic cell lines. Human acute myeloid leukemia (AML) cell lines, KG-1 and HL-60, were cultured. We searched for the gene expression of the major RAS components in KG-1 and HL-60 cell lines by quantitative real-time polymerase chain reaction analysis (qRT-PCR). Angiotensin-converting enzyme I (ACE I) and ACE II mRNA expressions were detected in KG-1 AML cell line. Relative expression of ACE I was higher than ACE II expression in this myeloid leukemic cells. Likewise, RENIN, angiotensinogen (ANGTS), and ACE I mRNA expressions were detected in HL-60 promyelocytic cell line. Relative RENIN expression was the highest, whereas ACE I expression was the lowest in HL-60 neoplastic myeloid cells. These findings indicate that there is a biologically active local RAS in the hematopoietic system in normal and pathological states.WoSScopu

The Impact Of Iron Overload On Transplant-Related Complications And Prognosis Of Acute Leukemias

The impacts of serum iron parameters and/or radiological evidence of systemic iron overload on the prognosis of hematopoietic stem cell transplantation (HSCT) in acute leukemia are controversial. Unfortunately, some of the studies evaluating iron overload in transplant setting did not precisely show the patients with iron overload, mainly due to ignoring consideration of transferrin saturation along with hyperferritinemia for elimination of non-iron overload etiologies of hyperferritinemia. The aim of this study is to assess the effect of iron overload on transplantation related complications and prognosis in acute leukemia. Patients who undergone allogeneic HSCT for acute leukemia in Hacettepe University Medical School Department of Hematology were screened retrospectively in order to find cases with serum iron tests within 9 months before transplant. The endpoints investigated were overall and disease-free survivals, acute and chronic graft-versus-host disease and veno-oclussive disease (VOD). There were 84 patients suitable for inclusion. When various ferritin plus transferrin saturation (TS) cut-off values were investigated for a possible relationship with major transplant-related complications/results only ferritin>2000 plus TS>45% was found to have an association with VOD at borderline significance (p=0.067). In conclusion, we observed a non-significant borderline relationship between iron overload and post-transplant VOD. We did not confirm other post-transplant complications reported in the literature. It must be noticed that although many studies intended to investigate the relationship between iron status and transplant outcomes, only a few of them have really looked for the effect of iron overload.WoSScopu

The Impact Of Jak1/Jak2 Inhibitor Ruxolitinib On The Spleen Size And Symptom Burden In Myeloproliferative Diseases

Ruxolitinib as a JAK1 and JAK2 inhibitor drug has recently been approved for the treatment of patients with high-or intermediate-risk myelofibrosis with symptomatic splenomegaly. Clinical development of ruxolitinib has currently focused on the Ph* negative myeloproliferative neoplastic disorders (MPN). The aim of this study is to assess the impact of ruxolitinib treatment on the clinical course of Ph* negative myeloproliferative disorders. Forty-three patients who were under ruxolitinib treatment and followed-up between years 1987-2015 in Hacettepe University Medical School Hematology Clinic and Ondokuz Mayis University Hematology Clinic with myeloproliferative disease without Philadephia chromosome translocation were retrospectively analyzed. The constitutional symptoms were decreased in 97% of patients after ruxolitinib treatment. The mean spleen sizes before and after ruxolitinib treatment were 229 +/- 35 versus 202 +/- 31 mm, respectively (p<0.001). In this study, we observed a reduction in spleen size after ruxolitinib treatment in Turkish patients with MPN and this reduction was statistically significant. Moreover, nearly all of the MPN patients' constitutional symptoms were improved. Those observations are concordant with other geographical MPN data obtained from different countries. Further experimental and clinical studies into the efficacy and safety of ruxolitinib in patients with MPN are necessary to elucidate its role in special subgroups of MPN patients, such as patients undergoing hematopoietic stem cell transplantation and the patients with vascular disorders such as hepatoportal thrombosis.WoSScopu

Local Hematopoietic Renin-Angiotensin System in Myeloid Versus Lymphoid Hematological Neoplastic Disorders

There is preliminary evidence that the local renin-angiotensin system (RAS) could affect neoplastic hematopoiesis. The aim of this study is to search messenger RNA (mRNA) expressions of the essential RAS elements in myeloid and lymphoid hematological neoplastic disorders. Forty-six patients with newly diagnosed myeloid (AML, biphenotypic leukemia, CML) or lymphoid (CLL, NHL, B-ALL, T-ALL) hematological disorders were included in the study. In the lymphoid group, the median expression values of RENIN, ACE1, ACE2 and ANGIOTENSINOGEN (ANGTS) mRNAs were 1.96%, 0.42%, 0.00% and 0.00%, respectively; in the myeloid group, 0.73%, 1.55%, 0.04% and 0.006%, respectively. In the lymphoid group, RENIN levels were significantly higher (p = 0.001), whereas ACE1 and ACE2 levels were significantly higher in the myeloid group (p values were 0.013 and 0.010, respectively). ANGTS levels were similar in both groups. In patients with non-ALL lymphoid malignancies, RENIN expressions were significantly higher when compared to ALL patients (p = 0.004). All patients with active disease had significantly higher RENIN mRNA expression levels than patients without active disease (2.03% vs 0.30%) (p = 0.034). The result of our present study indicates that the activities of local RAS may differ in distinct disease states such as leukemia and lymphomas.WoSScopu

Generic Imatinib Mesylate is as Effective as Original Glivec in the Clinical Management of CML

Unsustainable drug prices in chronic myeloid leukemia (CML) and cancer may be causing harm to patients. The aim of this multi-center study is to assess the efficacy of generic imatinib mesylate (IM) over Glivec in terms of hematological, cytogenetic, and molecular responses in CML. The data of 120 CML patients, who were treated with generic or original form of IM, were obtained from six different hematology clinics in Turkey between the years of 2009-2014 and analyzed retrospectively. Initial evaluation revealed that only one patient who was using original molecule switched to second generation tyrosine kinase inhibitor (TKI). In this period, hematological response(HR) was observed in 99.2% of the patients, cytogenetic response (CR) was observed in 88.7% of the patients (47 of 53), and molecular response (MR) was observed in 75% of the patients. Clinicians had a tendency to prefer generic molecules in each sequent visit, and this switch rate was statistically significant (p<0.001). 11 patients, who were using original molecules during all cohorts, switched to second generation TKI. On the other hand, only one patient, who was using generic molecules, switched to second generation TKI. Our paper may help to clarify the doubts about the efficacy of generic IM compared to original molecule. In our study we did not find any significant difference in HR, CR, and MR for original and generic drugs in each visit. Herein, we find low rates of need to switch to second generation TKIs with generic IM and no difference in treatment responses between generic and original molecules that confirms the non-inferiority of generic TKIs over original molecules