Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells

Diana Saleiro; Ewa M. Kosciuczuk; Mariafausta Fischietti; Ricardo E. Perez; G. Sohae Yang; Frank Eckerdt; Elspeth M. Beauchamp; Ye Hou; Qixuan Wang; Rona Singer Weinberg; Eleanor N. Fish; Feng Yue; Ronald Hoffman; Leonidas C. Platanias

doi:10.1158/2767-9764.CRC-23-0010

Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells

Diana Saleiro, Ewa M. Kosciuczuk, Mariafausta Fischietti, Ricardo E. Perez, G. Sohae Yang, Frank Eckerdt, Elspeth M. Beauchamp, Ye Hou, Qixuan Wang, Rona Singer Weinberg, Eleanor N. Fish, Feng Yue, Ronald Hoffman, Leonidas C. Platanias^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Interferons (IFNs) are cytokines with potent antineoplastic and antiviral properties. IFNα has significant clinical activity in the treatment of myeloproliferative neoplasms (MPN), but the precise mechanisms by which it acts are not well understood. Here, we demonstrate that chromatin assembly factor 1 subunit B (CHAF1B), an Unc-51-like kinase 1 (ULK1)-interactive protein in the nuclear compartment of malignant cells, is overexpressed in patients with MPN. Remarkably, targeted silencing of CHAF1B enhances transcription of IFNα-stimulated genes and promotes IFNα-dependent antineoplastic responses in primary MPN progenitor cells. Taken together, our findings indicate that CHAF1B is a promising newly identified therapeutic target in MPN and that CHAF1B inhibition in combination with IFNα therapy might offer a novel strategy for treating patients with MPN.

Original language	English (US)
Pages (from-to)	943-951
Number of pages	9
Journal	Cancer Research Communications
Volume	3
Issue number	5
DOIs	https://doi.org/10.1158/2767-9764.CRC-23-0010
State	Published - May 2023

ASJC Scopus subject areas

Oncology
Cancer Research
General Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/2767-9764.CRC-23-0010

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Saleiro, D., Kosciuczuk, E. M., Fischietti, M., Perez, R. E., Yang, G. S., Eckerdt, F., Beauchamp, E. M., Hou, Y., Wang, Q., Weinberg, R. S., Fish, E. N., Yue, F., Hoffman, R., & Platanias, L. C. (2023). Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells. Cancer Research Communications, 3(5), 943-951. https://doi.org/10.1158/2767-9764.CRC-23-0010

@article{586de6e95c5145b7adee485ce2b151e1,

title = "Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells",

abstract = "Interferons (IFNs) are cytokines with potent antineoplastic and antiviral properties. IFNα has significant clinical activity in the treatment of myeloproliferative neoplasms (MPN), but the precise mechanisms by which it acts are not well understood. Here, we demonstrate that chromatin assembly factor 1 subunit B (CHAF1B), an Unc-51-like kinase 1 (ULK1)-interactive protein in the nuclear compartment of malignant cells, is overexpressed in patients with MPN. Remarkably, targeted silencing of CHAF1B enhances transcription of IFNα-stimulated genes and promotes IFNα-dependent antineoplastic responses in primary MPN progenitor cells. Taken together, our findings indicate that CHAF1B is a promising newly identified therapeutic target in MPN and that CHAF1B inhibition in combination with IFNα therapy might offer a novel strategy for treating patients with MPN.",

author = "Diana Saleiro and Kosciuczuk, {Ewa M.} and Mariafausta Fischietti and Perez, {Ricardo E.} and Yang, {G. Sohae} and Frank Eckerdt and Beauchamp, {Elspeth M.} and Ye Hou and Qixuan Wang and Weinberg, {Rona Singer} and Fish, {Eleanor N.} and Feng Yue and Ronald Hoffman and Platanias, {Leonidas C.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors.",

year = "2023",

month = may,

doi = "10.1158/2767-9764.CRC-23-0010",

language = "English (US)",

volume = "3",

pages = "943--951",

journal = "Cancer Research Communications",

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T1 - Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells

AU - Saleiro, Diana

AU - Kosciuczuk, Ewa M.

AU - Fischietti, Mariafausta

AU - Perez, Ricardo E.

AU - Yang, G. Sohae

AU - Eckerdt, Frank

AU - Beauchamp, Elspeth M.

AU - Hou, Ye

AU - Wang, Qixuan

AU - Weinberg, Rona Singer

AU - Fish, Eleanor N.

AU - Yue, Feng

AU - Hoffman, Ronald

AU - Platanias, Leonidas C.

PY - 2023/5

Y1 - 2023/5

N2 - Interferons (IFNs) are cytokines with potent antineoplastic and antiviral properties. IFNα has significant clinical activity in the treatment of myeloproliferative neoplasms (MPN), but the precise mechanisms by which it acts are not well understood. Here, we demonstrate that chromatin assembly factor 1 subunit B (CHAF1B), an Unc-51-like kinase 1 (ULK1)-interactive protein in the nuclear compartment of malignant cells, is overexpressed in patients with MPN. Remarkably, targeted silencing of CHAF1B enhances transcription of IFNα-stimulated genes and promotes IFNα-dependent antineoplastic responses in primary MPN progenitor cells. Taken together, our findings indicate that CHAF1B is a promising newly identified therapeutic target in MPN and that CHAF1B inhibition in combination with IFNα therapy might offer a novel strategy for treating patients with MPN.

AB - Interferons (IFNs) are cytokines with potent antineoplastic and antiviral properties. IFNα has significant clinical activity in the treatment of myeloproliferative neoplasms (MPN), but the precise mechanisms by which it acts are not well understood. Here, we demonstrate that chromatin assembly factor 1 subunit B (CHAF1B), an Unc-51-like kinase 1 (ULK1)-interactive protein in the nuclear compartment of malignant cells, is overexpressed in patients with MPN. Remarkably, targeted silencing of CHAF1B enhances transcription of IFNα-stimulated genes and promotes IFNα-dependent antineoplastic responses in primary MPN progenitor cells. Taken together, our findings indicate that CHAF1B is a promising newly identified therapeutic target in MPN and that CHAF1B inhibition in combination with IFNα therapy might offer a novel strategy for treating patients with MPN.

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SN - 2767-9764

VL - 3

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JO - Cancer Research Communications

JF - Cancer Research Communications

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Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells

Abstract

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UN SDGs

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