From the Journals

PDPK1 could be novel target in MCL


 

FROM EXPERIMENTAL HEMATOLOGY

Researchers may have found a new therapeutic approach for treating mantle cell lymphoma (MCL) by targeting 3-phosphoinositide-dependent protein kinase 1 (PDPK1).

Saori Maegawa and colleagues at Kyoto Prefectural University of Medicine in Japan, evaluated PDPK1 activity in patient-derived primary B-cell lymphoma cells by immunohistochemical staining of p-PDPK1Ser241 (p-PDPK1) in tissue specimens from seven patients with MCL, six patients with diffuse large B-cell lymphoma, and five patients with follicular lymphoma. All specimens were biopsied at initial diagnosis, before starting treatment.

Mantle cell lymphoma histology Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

Mantle cell lymphoma

All 18 cases were moderately to strongly positive for p-PDPK1 regardless of disease subtype, stage, or risk. Tumor cells that were positive for CD5 and CCND1 were also positive for p-PDPK1 in the seven patients with MCL. This suggests that PDPK1 activation could be involved in disease development in most B-cell non-Hodgkin lymphomas, the researchers noted.

“Our study showed that PDPK1 inhibition caused inactivation of RSK2-NTKD, as well as the decrease of total RSK2 protein, but not of AKT, in MCL-derived cells,” the researchers wrote in Experimental Hematology. “This implies that RSK2 activity is mainly regulated by PDPK1 at both the transcriptional expression and post-translational levels, but AKT activity is regulated by a signaling pathway that does not interact with a PDPK1-mediated pathway in MCL.”

If a PDPK1 inhibitor is pursued as clinical target, the researchers said careful monitoring for hyperglycemia may be required since impaired glucose metabolism is commonly seen with AKT inhibitors. Future research in MCL could also be directed toward the targeting of RSK2-NTKD, the researchers wrote.

SOURCE: Maegawa S et al. Exp Hematol. 2018 Mar;59:72-81.e2.

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