Structure, signal transduction, activation, and inhibition of integrin αIIbß3.

Integrins are heterodimeric receptors comprising α and ß subunits. They are expressed on the cell surface and play key roles in cell adhesion, migration, and growth. Several types of integrins are expressed on the platelets, including αvß3, αIIbß3, α2ß1, α5ß1, and α6ß1. Among these, physically αIIbß3 is exclusively expressed on the platelet surface and their precursor cells, megakaryocytes. αIIbß3 adopts at least three conformations: i) bent-closed, ii) extended-closed, and iii) extended-open. The transition from conformation i) to iii) occurs when αIIbß3 is activated by stimulants. Conformation iii) possesses a high ligand affinity, which triggers integrin clustering and platelet aggregation. Platelets are indispensable for maintaining vascular system integrity and preventing bleeding. However, excessive platelet activation can result in myocardial infarction (MI) and stroke. Therefore, finding a novel strategy to stop bleeding without accelerating the risk of thrombosis is important. Regulation of αIIbß3 activation is vital for this strategy. There are a large number of molecules that facilitate or inhibit αIIbß3 activation. The interference of these molecules can accurately control the balance between hemostasis and thrombosis. This review describes the structure and signal transduction of αIIbß3, summarizes the molecules that directly or indirectly affect integrin αIIbß3 activation, and discusses some novel antiαIIbß3 drugs. This will advance our understanding of the activation of αIIbß3 and its essential role in platelet function and tumor development.

Acquired immune thrombotic thrombocytopenic purpura (TTP) associated with inactivated COVID-19 vaccine CoronaVac.

Corona virus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the whole world. Acquired thrombotic thrombocytopenic purpura (TTP) has been reported after administration of mRNA- or adenoviral vector-based COVID-19 vaccines, including Ad26.COV2-S, BNT162b2, mRNA-1273, and ChAdOx1 nCov-19. However, whether inactivated vaccines, such as CoronaVac, could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are unknown. In this study, two cases were reported. Both cases developed TTP after the second CoronaVac vaccination shot, but not the first. They demonstrated symptoms of fever, neurological abnormalities, renal dysfunction, thrombocytopenia, and hemolysis. Both patients achieved complete remission through several sessions of plasma exchanges and immune suppression. The incidence of TTP in Nanjing area was analyzed. The number of patients with TTP was 12 in 2019, 6 in 2020, 16 in 2021, and 19 in 2022. To the authors' knowledge, this report is the first report of TTP associated with inactivated COVID-19 vaccine (CoronaVac). The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based ones. Timely plasma exchange is a vital treatment for CoronaVac-related TTP, similar to activated vaccine-related TTP.

Biomarkers as targets for CAR-T/NK cell therapy in AML.

The most common kind of acute leukemia in adults is acute myeloid leukemia (AML), which is often treated with induction chemotherapy regimens followed by consolidation or allogeneic hematopoietic stem cell transplantation (HSCT). However, some patients continue to develop relapsed or refractory AML (R/R-AML). Small molecular targeted drugs require long-time administration. Not all the patients hold molecular targets. Novel medicines are therefore needed to enhance treatment outcomes. T cells and natural killer (NK) cells engineered with chimeric antigen receptors (CARs) that target antigens associated with AML have recently been produced and are currently being tested in both pre-clinical and clinical settings. This review provides an overview of CAR-T/NK treatments for AML.

Coexistence of diffuse large B-cell lymphoma, acute myeloid leukemia, and untreated lymphoplasmacytic lymphoma/waldenström macroglobulinemia in a same patient: A case report.

BACKGROUND: The Coexistence of myeloid and lymphoid malignancies is rare. Myeloid leukemia occurs more frequently as a secondary event in patients receiving chemotherapy agents for lymphoid malignancies. Synchronous diagnoses of diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML), and untreated lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) in the same patient have not been reported. Here we report one such case. CASE SUMMARY: An 89-year-old man had a chest wall mass histopathologically diagnosed as DLBCL. The bone marrow and peripheral blood contained two groups of cells. One group of cells fulfilled the criteria of AML, and the other revealed the features of small B lymphocytic proliferative disorder, which we considered LPL/WM. Multiple chromosomal or genetic changes were detected in bone marrow mononuclear cells, including ATM deletion, CCND1 amplification, mutations of MYD88 (L265P) and TP53, WT1 overexpression, and fusion gene of BIRC2-ARAP1, as well as complex chromosomal abnormalities. The patient refused chemotherapy because of old age and died of pneumonia 1 mo after the final diagnosis. CONCLUSION: The coexistence of DLBCL, AML, and untreated LPL/WM in the same patient is extremely rare, which probably results from multiple steps of genetic abnormalities. Asymptomatic LPL/WM might have occurred first, then myelodysplastic syndrome-related AML developed, and finally aggressive DLBCL arose. Therefore, medical staff should pay attention to this rare phenomenon to avoid misdiagnoses.