摘要
Aim:The main goal of this study was to elucidate at the transcript level the tyrosine kinase expression profiles of primary leukemia cells from mixed lineage leukemia 1 gene rearranged(KMT2A/MLL-R+)acute myeloid leukemia(AML)and acute lymphoblastic leukemia(ALL)patients.Methods:We evaluated protein tyrosine kinase(PTK)gene expression profiles of primary leukemic cells in KMT2A/MLL-R+AML and ALL patients using publicly available archived datasets.Results:Our studies provided unprecedented evidence that the genetic signatures of KMT2A/MLL-R+AML and ALL cells are characterized by transcript-level overexpression of specific PTK.In infants,children and adults with KMT2A/MLL-R+ALL,as well as pediatric patients with KMT2A/MLL-R+AML,the gene expression levels for FLT3,BTK,SYK,JAK2/JAK3,as well as several SRC family PTK were differentially amplified.In adults with KMT2A/MLLR+AML,the gene expression levels for SYK,JAK family kinase TYK2,and the SRC family kinases FGR and HCK were differentially amplified.Conclusion:These results provide new insights regarding the clinical potential of small molecule inhibitors of these PTK,many of which are already FDA/EMA-approved for other indications,as components of innovative multimodality treatment platforms against KMT2A/MLL-R+acute leukemias.
