Fms-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase constitutively expressed by acute myeloid leukaemia (AML) blasts. In addition, 25% of AML patients harbour a FLT3-ITD mutation, associated with inferior outcome due to increased relapse rate. Relapse might be propagated by interactions between AML blasts and the bone marrow microenvironment. Besides cellular elements of the microen...

FMS-like tyrosine kinase 3 with internal tandem duplication (FLT3 ITD) is an important oncoprotein in acute myeloid leukemia (AML). Owing to its constitutive kinase activity FLT3 ITD partially accumulates at endomembranes, a feature shared with other disease-associated, mutated receptor tyrosine kinases. Because Ras proteins also transit through endomembranes we have investigated the possible e...

Classical cadherin adhesion molecules can function as adhesion-activated cell-signaling receptors. One key target for cadherin signaling is the lipid kinase phosphoinositide (PI) 3-kinase, which is recruited to cell-cell contacts and activated by E-cadherin. In this study, we sought to identify upstream factors necessary for E-cadherin to activate PI 3-kinase signaling. We found that inhibition...

Objective: Glucosylceramide (GC) synthesized by glucosylceramide synthase (GCS) favors cell survival and proliferation in many cancers. However, it’s role Fms-like tyrosine kinase 3 (FLT3) non-mutant Acute Myeloid Leukemia (AML) pathogenesis is not clarified. Midostaurin, a multi-kinase inhibitor, clinically benefits FLT3-mutated AML, however, its clinical efficacy under-estimated FLT3 AML. Thi...

Frontline acute myeloid leukemia (AML) treatment is determined by a combination of patient and genetic factors. This includes fitness (i.e., comorbidities that increase the risk treatment-related mortality) characteristics, including cytogenetic events gene mutations. In older unfit patients, standard care typically venetoclax (VEN) combined with hypomethylating agents (HMA). Recently, several ...

Response to Are Aldosterone Levels Inappropriately Low in Preeclampsia? Verdonk et al1 raise an interesting hypothesis that increased angiotensin II sensitivity and angiotensin II type 1 receptor autoantibodies in preeclampsia may not lead to inappropriately lower aldosterone levels, a hypothesis not supported by both experimental and clinical studies. In humans, aldosterone levels are relative...

Insulin receptor substrate-2 (IRS-2) is phosphorylated on tyrosine by a number of cytokine receptors and is implicated in the activation of phosphatidylinositol 3'-kinase (PI3-kinase). Here, we demonstrate that induction of granulocytic differentiation of human promyeloid HL-60 cells leads to an increase in the amount of IRS-2 that is phosphorylated in response to insulin-like growth factor (IG...