SHIPi improves hematologic recovery after chemotherapy

The use of recombinant growth factors has led to improved hematopoietic function after chemotherapy, but hematologic and immune complications still occur after chemotherapy which can be life-threatening. Here we show that pan-SHIPi compounds can induce endogenous G-CSF and TPO production in vivo and can also increase host survival after a lethal fungal challenge. In addition, we show that consistent with their ability to induce G-CSF, pan-SHIPi compounds can promote increased granulopoiesis in normal mice and speed recovery of neutrophil counts after chemotherapy. We also report the identification of a novel SHIP1-selective inhibitor, A32, that also increases steady state production of both G-CSF and TPO. These findings indicate small molecule inhibitors of SHIP1 can promote hematologic recovery after myeloablative chemotherapy and are a unique means to induce endogenous production of multiple growth factors that promote hematologic recovery.

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Publication Details

Journal
Molecular Medicine
Published
2025-10-21
DOI
https://doi.org/10.1186/s10020-025-01383-3
Primary Topic
Antifungal resistance and susceptibility
Type
article
Field-Weighted Citation Impact
0.00

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article

SHIPi improves hematologic recovery after chemotherapy

Shawn Dormann, Denzil Bernard, Angela Pacherille, David Sancho et al.
Molecular Medicine
Antifungal resistance and susceptibility
article

SHIPi improves hematologic recovery after chemotherapy

Shawn Dormann, Denzil Bernard, Angela Pacherille, David Sancho, William G. Kerr, Shea T. Meyer, Carlos del Fresno, Sandra Fernandes, Brian Walker, Chiara Pedicone, John D. Chisholm, Bonnie B. Toms, Otto M. Dungan
article en

Abstract

The use of recombinant growth factors has led to improved hematopoietic function after chemotherapy, but hematologic and immune complications still occur after chemotherapy which can be life-threatening. Here we show that pan-SHIPi compounds can induce endogenous G-CSF and TPO production in vivo and can also increase host survival after a lethal fungal challenge. In addition, we show that consistent with their ability to induce G-CSF, pan-SHIPi compounds can promote increased granulopoiesis in normal mice and speed recovery of neutrophil counts after chemotherapy. We also report the identification of a novel SHIP1-selective inhibitor, A32, that also increases steady state production of both G-CSF and TPO. These findings indicate small molecule inhibitors of SHIP1 can promote hematologic recovery after myeloablative chemotherapy and are a unique means to induce endogenous production of multiple growth factors that promote hematologic recovery.

Molecular MedicineVol. 31(1)
SUNY Upstate Medical University (US), Hospital Universitario La Paz (ES), Spanish National Centre for Cardiovascular Research (ES), Hospital La Paz Institute for Health Research (ES), Healthwise (US), Spanish National Centre for Cardiovascular Research (ES), Syracuse University (US)
State University of New York, National Institutes of Health
Openalex Percentile: Top 65%
Antifungal resistance and susceptibility
DOIOpen Access PDFOpenAlex
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