Adding ruxolitinib or other interleukin-7 (IL7) receptor/JAK/STAT signaling inhibitors appears to enhance glucocorticoid efficacy in a subset of T-cell acute lymphoblastic leukemia (T-ALL) patients, according to a recent study. Among the findings:
- Glucocorticoid resistance is present at diagnosis in early thymic precursor (ETP) T-ALLs, as well as in a subset of non-ETP T-ALLs.
- Glucocorticoid resistant non-ETP T-ALLs are characterized by strong induction of JAK/STAT signaling in response to IL7 stimulation.
- Removing IL7 or inhibiting JAK/STAT signaling sensitizes these T-ALLs--as well as a subset of ETP T-ALLs--to glucocorticoids.
- The combination of dexamethasone and ruxolitinib altered the balance between pro- and anti-apoptotic factors in samples with IL7-dependent glucocorticoid resistance, but not in samples with IL7-independent glucocorticoid resistance.
Delgado-Martin C, Meyer L, Huang B, et al. JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias. [Published online ahead of print May 9, 2017]. Leukemia. doi:10.1038/leu.2017.136.
This Week's Must Reads
Must Reads in Hematologic Malignancies
Long-term ibrutinib data in older patients, Barr PM et al. Haematologica. 2018;103(9):1502-10
Prognostic Score System for Patients with PMF, J Clin Oncol; ePub 2017 Dec 9; Gugliemelli, et al
These Patients Are More Apt to Be Depressed, Ann Hematol; ePub 2017 Dec 7; Shreders, et al
Survival Length Shortest in These Patients with MF, Eur J Haematol; ePub 2017 Dec 11; Masarova, et al
The Value of Ruxolitinib Before and After AlloSCT, Blood; ePub 2017 Dec 7; Poulose, Malysz, et al