LMO2 Expression Is Frequent in T-lymphoblastic Leukemia and Correlates With Survival, Regardless of T-cell Stage

Authors

Kerri-Ann Latchmansingh
Xiaoqiong Wang
Ramiro E Verdun
Mario L Marques-Piubelli
Francisco Vega
M James You
Jennifer Chapman
Izidore S Lossos

Publication Date

9-1-2022

Journal

Modern Pathology

Abstract

T- lymphoblastic leukemia/lymphoma (T-LL) is an aggressive malignancy of immature T-cells with poor overall survival (OS) and in need of new therapies. LIM-domain only 2 (LMO2) is a critical regulator of hematopoietic cell development that can be overexpressed in T-LL due to chromosomal abnormalities. Deregulated LMO2 expression contributes to T-LL development by inducing block of T-cell differentiation and continuous thymocyte self-renewal. However, LMO2 expression and its biologic significance in T-LL remain largely unknown. We analyzed LMO2 expression in 100 initial and follow-up biopsies of T-LL from 67 patients, including 31 (46%) early precursor T-cell (ETP)-ALL, 26 (39%) cortical and 10 (15%) medullary type. LMO2 expression was present in 50 (74.6%) initial biopsies with an average of 87% positive tumor cells (range 30-100%). LMO2 expression in ETP, medullary and cortical T-LLs was not statistically different. In patients with biopsies after initial therapy, LMO2 expression was stable. LMO2 expression was associated with longer OS (p = 0.048) regardless of T-lymphoblast stage or other clinicopathologic features. These findings indicate that LMO2 is a promising new prognostic marker that could predict patients' outcomes and potentially be targeted for novel chemotherapy, i.e. PARP1/2 inhibitors, which have been shown to enhance chemotherapy sensitivity in LMO2 expressing diffuse large B cell lymphoma (DLBCL) tumors by decreasing DNA repair efficiency.

Keywords

Adaptor Proteins, Signal Transducing, Humans, LIM Domain Proteins, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Proto-Oncogene Proteins, T-Lymphocytes

DOI

10.1038/s41379-022-01063-1

PMID

35322192

PMCID

PMC9427670

PubMedCentral® Posted Date

3-1-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes