Clinical Edge

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Adding Ruxolitinib to Certain Patients with T-ALL

Leukemia; ePub 2017 May 9; Delgado-Martin, et al

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.

Citation:

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.