Background: Heterogeneity of leukemia-initiating cells (LICs) is a major obstacle in acute myeloid leukemia (AML) therapy. Accumulated evidence indicates that the coexistence of multiple types of LICs with different pathogenicity in the same individual is a common feature in AML. However, the functional heterogeneity including the drug response of coexistent LICs remains unclear. Therefore, this study aimed to clarify the intra-heterogeneity in LICs that can help predict leukemia behavior and develop more effective treatments.

PTPN2 (protein tyrosine phosphatase non-receptor 2), also called TCPTP (T cell protein tyrosine phosphatase), is a member of the PTP family signaling proteins. Phosphotyrosine-based signaling of this non-transmembrane protein is essential for regulating cell growth, development, differentiation, survival, and migration. In particular, PTPN2 received researchers’ attention when Manguso et al. identified PTPN2 as a cancer immunotherapy target using in vivo CRISPR library screening. In this review, we attempt to summarize the important functions of PTPN2 in terms of its structural and functional properties, inflammatory reactions, immunomodulatory properties, and tumor immunity. PTPN2 exerts synergistic anti-inflammatory effects in various inflammatory cells and regulates the developmental differentiation of immune cells. The diversity of PTPN2 effects in different types of tumors makes it a potential target for tumor immunotherapy.

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Background and study aims Although ulcerative colitis (UC) incidence is increasing in China, there are few reports on risk factors. We conducted a case‒control study in Tianjin, China, to assess potential risk factors for the development, extent and severity of UC. Methods 361 UC patients and 1444 controls with similar social backgrounds were screened by detailed questionnaires and corresponding endoscopic findings in Tianjin's colorectal cancer screening program from 2012 to 2020. Basic demographic characteristics were compared using the chi-square test, and multivariate analysis was conducted by conditional logistic regression models. Results Multivariate analysis showed the risk factors for UC were male sex (OR = 1.83, 95% Cl: 1.27-2.63) and history of mucus and blood in stool (OR = 3.25 95% Cl: 2.24 4.68). For lesion extent and lesion severity, men and patients with history of mucus and blood in stool were more likely to have larger and more severe UC lesions. Advanced age, BMI≥25, current smoking status, regular exercise, a history of first-degree relatives with bowel cancer, and a history of chronic constipation were indicated as protective factors for UC. Conclusions Our study demonstrates that different environmental factors influence different clinical pathways in the initiation and progression of UC. Avoidance of environmental variables associated with disease risk leads to better clinical outcomes.

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