Objective: To study the clinicopathologic features and prognostic significance of ZAP-70 protein expression in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Methods: The histologic features of 52 cases of CLL/SLL with lymph node and/or bone marrow biopsies performed were retrospectively reviewed. Immunohistochemical study using EliVision for ZAP-70 protein was adopted.
Results: The lymph nodes of the 12 cases studied showed effacement of the nodal architecture and was replaced by a monotonous infiltration of small lymphoid cells. Among them, proliferation centers were identified in 6 cases. Similar morphologic pattern was seen in the 40 bone marrow biopsy samples, but no proliferation center formation obtained. The infiltration pattern of tumor cells in the bone marrow were further subdivided into nodular (n = 9), interstitial (n = 3), mixed (n = 9) and diffuse types (n = 19). There was no significant difference found on survival rates between the diffuse infiltration and non-diffuse infiltration groups (Fisher's exact test, P = 0.199). ZAP-70 protein was mainly located in the cytoplasm and nuclei of lymphoma cells. There were 21 cases (40.4%) positive for ZAP-70 and among them, 11 died of this disease or the related infections. On the other hand, ZAP-70 was negative in 31 cases (59.6%) and only 4 of them died of this disease or related infections. The overall survival in ZAP-70-negative group was higher than that of the ZAP-70-positive group (59 months versus 39 months, chi(2) = 6.991, P = 0.008). Follow-up information was available in 51 patients. Among the 21 dead cases, 15 died of CLL/SLL or the related infection.
Conclusion: A positive expression of ZAP-70 protein in CLL/SLL suggests a poor prognosis.
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Blood
December 2024
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
Deuterated ("heavy") water labeling in patients with chronic lymphocytic leukemia (CLL) demonstrates that IGHV unmutated and ZAP-70+ patients have higher blood and tissue CLL death rates on ibrutinib therapy, resulting in lower measurable residual disease levels with long-term ibrutinib treatment. This trial was registered at www.clinicaltrials.
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September 2024
Department of Immunology, College of Basic Medicine, Chongqing Medical University, Chongqing 400010, China; Chongqing Key Laboratory of Tumor Immune Regulation and Immune Intervention, Chongqing 400010, China. Electronic address:
For adoptive therapy with T cell receptor engineered T (TCR-T) cells, the quantity and quality of the final cell product directly affect their anti-tumor efficacy. The post-transfer efficacy window of TCR-T cells is keen to optimizing attempts during the manufacturing process. Cbl-b is a E3 ubiquitin ligase previously shown with critical negative impact in T cell functions.
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August 2024
School of Life Science and Biochemistry, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, Liaoning Province, China.
Heart failure (HF) is a terminal condition of multiple cardiovascular disorders. Cancer is a deadly disease worldwide. The relationship between HF and cancer remains poorly understood.
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Department of Biology, Zand Institute of Higher Education, Shiraz, Iran.
Background: The apparent lack of additional missense mutations data on mixed-phenotype leukemia is noteworthy. Single amino acid substitution by these non-synonymous single nucleotide variations can be related to many pathological conditions and may influence susceptibility to disease. This case-control study aimed to unravel whether the ZAP70 missense variant (rs104893674 (C > A)) underpinning mixed-phenotype leukemia.
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August 2024
Laboratory of Immune Cell Biology, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
The serine/threonine phosphatase calcineurin is a component of the T cell receptor (TCR) signalosome, where it promotes T cell activation by dephosphorylating Lck. Using small interfering RNA (siRNA)-mediated knockdown and CRISPR-Cas9-targeted genetic disruption of the calcineurin A chain α and β isoforms, we find that calcineurin also functions as an adaptor in TCR-signaled human T cells. Unlike inhibition of its phosphatase activity, in the absence of calcineurin A, TCR signaling results in attenuated actin rearrangement, markedly reduced TCR-Lck microcluster formation and recruitment of the adaptor RhoH, and diminished phosphorylation of critical targets downstream of Lck such as TCRζ and ZAP-70.
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