The efficient treatment of hematological malignancies as Acute Myeloid Leukemia, myelofibrosis and Chronic Myeloid Leukemia, requires the elimination of cancer-initiating cells and the prevention of disease relapse through targeting pathways that stimulate generation and maintenance of these cells. In mammals, inhibition of Smoothened, the key mediator of the Hedgehog signaling pathway, reduces...

Myeloproliferative diseases such as acute myeloid leukemia (AML), chronic myeloid leukemia (CML) , and polycythemia vera (PV) are now generally considered to be clonal disorders originating in abnormal stern cells (Wiggans et al. 1978; Fialkow et al. 1967, 1977; Adamson et al. 1976; McCuIloch and Till 1977; McCuIloch 1979). A growth advantage typically displayed by the abnormal clone appears to...

Nitric oxide (NO) is a molecule required for many physiological functions, produced from L-arginine by NO synthases (NOS). It is a free radical, producing many reactive intermediates that account for its bioactivity. Sustained induction of the inducible form of NOS (iNOS) in chronic inflammation may be mutagenic, through NO-mediated DNA damage or hindrance to DNA repair, and thus potentially ca...

Abstract Resistance remains the major clinical challenge for therapy of Philadelphia chromosome–positive (Ph+) leukemia. With exception ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit common “gatekeeper” mutation T315I. Here we investigated therapeutic potential crizotinib, a TKI targeting ALK and ROS1 in non-small cell lung cancer patients, which inhibited also ...

INTRODUCTION In patients with chronic myeloid leukemia, tyrosine kinase inhibitors suppress the BCR-ABL+ clone and often induce complete molecular remissions. Megakaryocytes in such patients have been shown to be derived from the BCR-ABL+ clone, and abnormal platelet function is frequent in chronic myeloid leukemia. However, little is known about the influence of modern targeted therapy on chro...

Chronic myeloid leukemia and systemic mastocytosis are myeloid neoplasms sharing a number of pathogenetic and clinical features. In both conditions, an aberrantly activated oncoprotein with tyrosine kinase activity, namely BCR-ABL1 in chronic myeloid leukemia, and mutant KIT, mostly KIT D816V, in systemic mastocytosis, is key to disease evolution. The appreciation of the role of such tyrosine k...

Acute myeloid leukemia (AML) is a type of poor prognosis hematological malignancies characterized by heterogeneous clonal expansion of myeloid progenitors. Leukemic stem cells are thought to form the majority of a cell population in minimal residual diseases (MRDs) which are resistant to current chemotherapeutic regimens and mediate disease relapse. Current therapeutic vaccine strategies have d...

Lapatinib is an oral-form dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR or ErbB/Her) superfamily members with anticancer activity. In this study, we examined the effects and mechanism of action of lapatinib on several human leukemia cells lines, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and acute lymphoblastic leukemia (ALL) cells. We fou...

Human cancers display substantial intratumoral genetic heterogeneity, which facilitates tumor survival under changing microenvironmental conditions. Tumor substructure and its effect on disease progression and relapse are incompletely understood. In the present study, a high-throughput method that uses neutral somatic mutations accumulated in individual cells to reconstruct cell lineage trees w...

Introduction: chronic myeloid leukemia is one of the major diseases, which cause death worldwide. Tyrosine kinase responsible for uncontrolled cell growth and block its function. Its inhibition a promising route to control out grow cells. The purpose our study involves docking human Abl with seven ciprofloxacin derivatives comparison results free energy binding positive (Imatinib).Methods: pres...