The FLT3 receptor tyrosine kinase is expressed in more than 90% of acute myelogeneous leukemias (AMLs), up to 30% of which carry an internal tandem duplication (ITD) within the FLT3 gene. Although varying duplication sites exist, most FLT3-ITDs affect a single protein domain. We analyzed the FLT3-ITD of an AML patient for encoding HLA class I-restricted immunogenic peptides. One of the tested p...

Duplogs, or intraspecies paralogs, constitute the important portion of eukaryote genomes and serve as a major source of functional innovation. We conducted detailed analyses of recently emerged animal duplogs. Genome data of three vertebrate species (Homo sapiens, Mus musculus, and Danio rerio), Caenorhabditis elegans, and two Drosophila species (Drosophila melanogaster and D. pseudoobscura) we...

The ATP-binding-cassette transmembrane transporters (ABC transporters) known from vertebrates belong to four major subfamilies: (1) the P-glycoproteins (Pgp); (2) the cystic fibrosis transmembrane conductance regulators (CFTR); (3) the Tap proteins encoded with the major histocompatibility complex of mammals; and (4) the peroxisomal membrane proteins. Both Pgp and CFTR have a structure suggesti...

FLT3 (fms-related tyrosine kinase 3) with tandem internal duplication (ITD) is a known adverse prognostic factor in normal karyotype acute myeloid leukemia (AML). Since we recently observed several patients with trisomy 8 (+8) and FLT3 positivity, we asked whether FLTD ITD carried any prognostic significance in sole trisomy 8. Trisomy 8 is the most frequent numerical aberration in AML, occurrin...

Constitutively activating mutations of FMS-like tyrosine kinase 3 (FLT3) occur in approximately one third of patients with acute myeloid leukemia (AML) and are associated with poor prognosis. Altered FLT3 signaling leads to antiapoptotic and proliferative signaling pathways. We recently showed that these mutations can also contribute to the differentiation arrest that characterizes leukemia. In...

Correspondence To the Editor: Sorafenib is a novel, orally available inhibitor of multiple kinases. It has been used in relapsed and refractory FMS‑like tyrosine kinase (FLT)‑3‑positive acute myeloid leukemia (AML) in recent years with favorable outcomes. Thyroiditis and hypothyroidism as side effects have been reported in treatment on renal cell cancer. [1] Here, we report a case of FLT3‑inter...

Constitutively activating mutations of FMS-like tyrosine kinase 3 (FLT3) occur in approximately one third of patients with acute myeloid leukemia (AML) and are associated with poor prognosis. Altered FLT3 signaling leads to antiapoptotic and proliferative signaling pathways. We recently showed that these mutations can also contribute to the differentiation arrest that characterizes leukemia. In...

In this issue of Blood, Dany et al demonstrate a critical role of the ceramideregulated signaling pathway in inducing mitophagy to cause cell death and overcome drug resistance of acute myeloid leukemia (AML) cells carrying internal tandem duplication (ITD) of the Fms-like tyrosine kinase 3 (FLT3) gene. Inhibition of FLT3-ITD signaling through altering ceramide-involved lipid metabolism provide...