CSRP2 transcript levels after consolidation therapy increase prognostic prediction ability in B-cell acute lymphoblastic leukaemia

Lei-Ming Cao; Ya-Lan  Zhou; Robert Peter Gale; Ya-Zhen Qin; Li-Xin  Wu; Ming-Yue Zhao; Xiao-Su Zhao; Yu-Hong Chen; Yu Wang; Hao Jiang; Qian Jiang; Ying-Jun Chang; Yan-Rong Liu; Lan-Ping Xu; Xiao-Hui Zhang; Xiao-Jun Huang; Guo-Rui  Ruan

doi:10.17305/bb.2023.9034

Authors

Lei-Ming Cao Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Ya-Lan Zhou Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China https://orcid.org/0000-0002-7059-8277
Robert Peter Gale Department of Immunology and Inflammation, Centre for Haematology, Imperial College of Science, Technology and Medicine, London, UK
Ya-Zhen Qin Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Li-Xin Wu Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Ming-Yue Zhao Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Xiao-Su Zhao Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Yu-Hong Chen Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Yu Wang Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Hao Jiang Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Qian Jiang Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Ying-Jun Chang Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Yan-Rong Liu Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Lan-Ping Xu Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Xiao-Hui Zhang Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China
Xiao-Jun Huang Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Academy for Advanced Interdisciplinary Studies, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Guo-Rui Ruan Peking University Institute of Hematology, Peking University People’s Hospital, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

DOI:

https://doi.org/10.17305/bb.2023.9034

Keywords:

Acute lymphoblastic leukaemia (ALL), relapse, measurable residual disease (MRD), cysteine and glycine-rich protein 2 (CSRP2), multi-parameter flow cytometry (MPFC)

Abstract

Quantification of measurable residual disease (MRD) correlates with the risk of leukemia recurrence in adults with B-cell acute lymphoblastic leukemia (ALL). However, it remains unknown whether collecting data on cysteine and glycine-rich protein 2 (CSRP2) transcript levels, after completing the second course of consolidation, improves prognosis prediction accuracy. A total of 204 subjects with B-cell ALL were tested for CSPR2 transcripts after completing the second course of consolidation using quantitative real-time polymerase chain reaction (qRT-PCR) and divided into high (N = 32) and low (N = 172) CSRP2 expression cohorts. In multivariable analyses, subjects with high expression of CSRP2 had a higher 5-year cumulative incidence of relapse (CIR) (hazard ratio [HR] = 2.57, 95% confidence interval [CI] 1.38-4.76; P = 0.003), lower 5-year relapse-free survival (RFS) (HR = 3.22, 95% CI 1.75-5.93; P < 0.001), and overall survival (OS) (HR = 4.59, 95% CI 2.64-7.99; P < 0.001) in the whole cohort, as well as in the multi-parameter flow cytometry (MPFC) MRD-negative cohort (for CIR, HR = 2.70, 95% CI 1.19-6.12; for RFS, HR = 4.37, 95% CI 1.94-9.85; for OS, HR = 4.90, 95% CI 2.43-9.90; all P < 0.05). Prognostic analysis showed that allogeneic hematopoietic stem cell transplantation (allo-HSCT) could significantly improve the prognosis of patients with high CSRP2 expression (allo-HSCT vs chemotherapy: 5-year CIR, 52% vs 91%; RFS, 41% vs 9%; OS, 38% vs 20%; all P < 0.05). Our data indicate that incorporating data from CSPR2 transcript levels to the MRD-testing at the end of the second course of consolidation therapy enhances prognosis prediction accuracy in adults with B-cell ALL.