JAK3 mutations and mitochondrial apoptosis resistance in T-cell acute lymphoblastic leukemia was written by Bodaar, Kimberly;Yamagata, Natsuko;Barthe, Anais;Landrigan, Jack;Chonghaile, Triona Ni;Burns, Melissa;Stevenson, Kristen E.;Devidas, Meenakshi;Loh, Mignon L.;Hunger, Stephen P.;Wood, Brent;Silverman, Lewis B.;Teachey, David T.;Meijerink, Jules P.;Letai, Anthony;Gutierrez, Alejandro. And the article was included in Leukemia in 2022.Reference of 16506-27-7 The following contents are mentioned in the article:
Resistance to mitochondrial apoptosis predicts inferior treatment outcomes in patients with diverse tumor types, including T-cell acute lymphoblastic leukemia (T-ALL). However, the genetic basis for variability in this mitochondrial apoptotic phenotype is poorly understood, preventing its rational therapeutic targeting. Using BH3 profiling and exon sequencing anal. of childhood T-ALL clin. specimens, we found that mitochondrial apoptosis resistance was most strongly associated with activating mutations of JAK3. Mutant JAK3 directly repressed apoptosis in leukemia cells, because its inhibition with mechanistically distinct pharmacol. inhibitors resulted in reversal of mitochondrial apoptotic blockade. Inhibition of JAK3 led to loss of MEK, ERK and BCL2 phosphorylation, and BH3 profiling revealed that JAK3-mutant primary T-ALL patient samples were characterized by a dependence on BCL2. Treatment of JAK3-mutant T-ALL cells with the JAK3 inhibitor tofacitinib in combination with a spectrum of conventional chemotherapeutics revealed synergy with glucocorticoids, in vitro and in vivo. These findings thus provide key insights into the mol. genetics of mitochondrial apoptosis resistance in childhood T-ALL, and a compelling rationale for a clin. trial of JAK3 inhibitors in combination with glucocorticoids for patients with JAK3-mutant T-ALL. This study involved multiple reactions and reactants, such as 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7Reference of 16506-27-7).
4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Imidazole is incorporated into many important biological compounds. The most pervasive is the amino acid histidine, which has an imidazole side-chain. Histidine is present in many proteins and enzymes, e.g. by binding metal cofactors, as seen in hemoglobin.Reference of 16506-27-7
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem