Publications by authors named "Sonu Kalyan"

5 Publications

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Inhibition of Bromodomain and Extra Terminal (BET) Domain Activity Modulates the IL-23R/IL-17 Axis and Suppresses Acute Graft--Host Disease.

Front Oncol 2021 15;11:760789. Epub 2021 Oct 15.

Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States.

Acute graft--host disease (GVHD) is the leading cause of non-relapse mortality following allogeneic hematopoietic cell transplantation. The majority of patients non-responsive to front line treatment with steroids have an estimated overall 2-year survival rate of only 10%. Bromodomain and extra-terminal domain (BET) proteins influence inflammatory gene transcription, and therefore represent a potential target to mitigate inflammation central to acute GVHD pathogenesis. Using potent and selective BET inhibitors Plexxikon-51107 and -2853 (PLX51107 and PLX2853), we show that BET inhibition significantly improves survival and reduces disease progression in murine models of acute GVHD without sacrificing the beneficial graft--leukemia response. BET inhibition reduces T cell alloreactive proliferation, decreases inflammatory cytokine production, and impairs dendritic cell maturation both and . RNA sequencing studies in human T cells revealed that BET inhibition impacts inflammatory IL-17 and IL-12 gene expression signatures, and Chromatin Immunoprecipitation (ChIP)-sequencing revealed that BRD4 binds directly to the IL-23R gene locus. BET inhibition results in decreased IL-23R expression and function as demonstrated by decreased phosphorylation of STAT3 in response to IL-23 stimulation in human T cells as well as in mouse donor T cells . Furthermore, PLX2853 significantly reduced IL-23R+ and pathogenic CD4+ IFNγ+ IL-17+ double positive T cell infiltration in gastrointestinal tissues in an acute GVHD murine model. Our findings identify a role for BET proteins in regulating the IL-23R/STAT3/IL-17 pathway. Based on our preclinical data presented here, PLX51107 will enter clinical trial for refractory acute GVHD in a Phase 1 safety, biological efficacy trial.
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http://dx.doi.org/10.3389/fonc.2021.760789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554203PMC
October 2021

Modulating endothelial cells with EGFL7 to diminish aGVHD after allogeneic bone marrow transplantation in mice.

Blood Adv 2021 Oct 15. Epub 2021 Oct 15.

Hopital Maisonneuve-Rosemont, Canada.

Acute graft versus host (aGVHD) is the second cause of death after allogeneic-hematopoietic stem cell transplant (allo-HSCT) underscoring the need for novel therapies. Based on previous work that endothelial cell dysfunction is present in aGVHD and that epidermal growth factor-like domain 7 (EGFL7) plays a significant role in decreasing inflammation by repressing endothelial cell activation and T cell migration, we hypothesized that increasing EGFL7 levels after allo-HSCT will diminish the severity of aGVHD. Here, we show that treatment with recombinant EGFL7 (rEGFL7) in two different murine models of aGVHD decreases aGVHD severity and improves survival in recipient mice after allogeneic transplantation with respect to controls without affecting graft versus leukemia effect. Furthermore, we showed that rEGFL7 treatment results in higher thymocytes, T, B and dendritic cells in recipient mice after allo-HSCT. This study constitutes a proof of concept of the ability of rEGFL7 therapy to reduce GHVD severity and mortality after allo-HSCT.
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http://dx.doi.org/10.1182/bloodadvances.2021005498DOI Listing
October 2021

Targeting BRD4 in acute myeloid leukemia with partial tandem duplication of the gene.

Haematologica 2021 09 1;106(9):2527-2532. Epub 2021 Sep 1.

The Ohio State University, Comprehensive Cancer Center, Columbus, OH, USA; Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH.

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http://dx.doi.org/10.3324/haematol.2020.271627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409020PMC
September 2021

Primary Stromal Sarcoma of Breast: A Rare Entity.

Iran J Pathol 2016 2;11(5):469-473. Epub 2017 Jan 2.

Dept. of Pathology, PGIMS, Rohtak (Haryana), India.

Primary soft tissue sarcomas of the breast constitute less than 5% of all soft tissue sarcomas and less than 1% of malignant breast cancers. The rarity of this tumor limits most studies to small retrospective case reviews and case reports. Primary breast sarcomas are locally aggressive tumors as evidenced by the high rate of local recurrence when excisional surgery is performed. A contemporary multidisciplinary approach to therapy including surgery, radiation, and chemotherapy is advocated. Herein, we report a case of 45-yr-old female, who presented with a large ulcerated breast mass and was diagnosed as carcinoma breast on fine needle aspiration. Modified radical masectomy was performed and was diagonsed with primary breast stromal sarcoma on histopathology, which is a rare entity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5604113PMC
January 2017

Disseminated invasive aspergillosis in a prolonged stay in the intensive care unit.

Autops Case Rep 2017 Jan-Mar;7(1):17-21. Epub 2017 Mar 30.

Department of Pathology - Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences - Rohtak/Haryana - India.

Aspergillus is a common cause of invasive mycosis, especially in immunocompromised individuals. We report the case of a 62-year-old male who was hospitalized after suffering severe physical injuries and died after few weeks of hospitalization. A medicolegal autopsy was conducted, and various organs were sent for histopathological examination of which heart, lungs, and kidneys showed extensive involvement by aspergillus. Thus, a diagnosis of disseminated invasive aspergillosis was made on autopsy, which itself is a rare entity. This case report illustrates a prolonged stay in the intensive care unit as a possible risk factor for the development of disseminated aspergillosis.
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http://dx.doi.org/10.4322/acr.2017.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5436917PMC
March 2017
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