Prognostic significance of cathepsin L expression in pediatric acute myeloid leukemia

Garima Pandey; Sameer Bakhshi; Bhaskar Thakur; Prerna Jain; Shyam S. Chauhan

doi:10.1080/10428194.2017.1422865

Prognostic significance of cathepsin L expression in pediatric acute myeloid leukemia

Garima Pandey, Sameer Bakhshi, Bhaskar Thakur, Prerna Jain, Shyam S. Chauhan

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

13 Scopus citations

Abstract

Overexpression of cathepsin L (CTSL), an endolysosomal cysteine protease, is associated with inferior survival of patients with various human malignancies. We evaluated the expression/activity of CTSL in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of 103 pediatric acute myeloid leukemia (AML) patients to assess its prognostic significance in this malignancy. Thirty-five healthy siblings of patients served as controls. Our results revealed significantly higher CTSL activity (p <.0001), protein (p <.05), and mRNA levels (p <.01) in both PBMCs and BMMCs of patients as compared with controls. BMMCs displayed higher activity of CTSL than PBMCs (p <.01). A dramatic reduction in CTSL activity was recorded after chemotherapy in a significant proportion (74%) of patients (p <.0001). By multivariate analysis, CTSL in BMMCs emerged as a strong independent prognostic marker for overall survival (OS) (p =.004). Thus, our results suggest the potential utility of CTSL in predicting the outcome of pediatric AML.

Original language	English (US)
Pages (from-to)	2175-2187
Number of pages	13
Journal	Leukemia and Lymphoma
Volume	59
Issue number	9
DOIs	https://doi.org/10.1080/10428194.2017.1422865
State	Published - Sep 2 2018
Externally published	Yes

Keywords

Cancer
PBMC
VEGF
bone marrow mononuclear cells
cystatin C
gene expression

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1080/10428194.2017.1422865

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title = "Prognostic significance of cathepsin L expression in pediatric acute myeloid leukemia",

abstract = "Overexpression of cathepsin L (CTSL), an endolysosomal cysteine protease, is associated with inferior survival of patients with various human malignancies. We evaluated the expression/activity of CTSL in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of 103 pediatric acute myeloid leukemia (AML) patients to assess its prognostic significance in this malignancy. Thirty-five healthy siblings of patients served as controls. Our results revealed significantly higher CTSL activity (p <.0001), protein (p <.05), and mRNA levels (p <.01) in both PBMCs and BMMCs of patients as compared with controls. BMMCs displayed higher activity of CTSL than PBMCs (p <.01). A dramatic reduction in CTSL activity was recorded after chemotherapy in a significant proportion (74%) of patients (p <.0001). By multivariate analysis, CTSL in BMMCs emerged as a strong independent prognostic marker for overall survival (OS) (p =.004). Thus, our results suggest the potential utility of CTSL in predicting the outcome of pediatric AML.",

keywords = "Cancer, PBMC, VEGF, bone marrow mononuclear cells, cystatin C, gene expression",

author = "Garima Pandey and Sameer Bakhshi and Bhaskar Thakur and Prerna Jain and Chauhan, {Shyam S.}",

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AU - Pandey, Garima

AU - Bakhshi, Sameer

AU - Thakur, Bhaskar

AU - Jain, Prerna

AU - Chauhan, Shyam S.

PY - 2018/9/2

Y1 - 2018/9/2

N2 - Overexpression of cathepsin L (CTSL), an endolysosomal cysteine protease, is associated with inferior survival of patients with various human malignancies. We evaluated the expression/activity of CTSL in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of 103 pediatric acute myeloid leukemia (AML) patients to assess its prognostic significance in this malignancy. Thirty-five healthy siblings of patients served as controls. Our results revealed significantly higher CTSL activity (p <.0001), protein (p <.05), and mRNA levels (p <.01) in both PBMCs and BMMCs of patients as compared with controls. BMMCs displayed higher activity of CTSL than PBMCs (p <.01). A dramatic reduction in CTSL activity was recorded after chemotherapy in a significant proportion (74%) of patients (p <.0001). By multivariate analysis, CTSL in BMMCs emerged as a strong independent prognostic marker for overall survival (OS) (p =.004). Thus, our results suggest the potential utility of CTSL in predicting the outcome of pediatric AML.

AB - Overexpression of cathepsin L (CTSL), an endolysosomal cysteine protease, is associated with inferior survival of patients with various human malignancies. We evaluated the expression/activity of CTSL in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of 103 pediatric acute myeloid leukemia (AML) patients to assess its prognostic significance in this malignancy. Thirty-five healthy siblings of patients served as controls. Our results revealed significantly higher CTSL activity (p <.0001), protein (p <.05), and mRNA levels (p <.01) in both PBMCs and BMMCs of patients as compared with controls. BMMCs displayed higher activity of CTSL than PBMCs (p <.01). A dramatic reduction in CTSL activity was recorded after chemotherapy in a significant proportion (74%) of patients (p <.0001). By multivariate analysis, CTSL in BMMCs emerged as a strong independent prognostic marker for overall survival (OS) (p =.004). Thus, our results suggest the potential utility of CTSL in predicting the outcome of pediatric AML.

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KW - cystatin C

KW - gene expression

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Prognostic significance of cathepsin L expression in pediatric acute myeloid leukemia

Abstract

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