Evolving strategies to overcome barriers in CAR-T cell therapy for acute myeloid leukemia.

Introduction: Acute myeloid leukemia (AML) is a complex and heterogeneous disease characterized by an aggressive clinical course and limited efficacious treatment options in the relapsed/refractory (R/R) setting. Chimeric antigen receptor (CAR)-modified T (CAR-T) cell immunotherapy is an investigational treatment strategy for R/R AML that has shown some promise. However, obstacles to successful CAR-T cell immunotherapy for AML remain.

The Intriguing Connections between von Willebrand Factor, ADAMTS13 and Cancer.

von Willebrand factor (VWF) is a complex and large protein that is cleaved by ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), and together they serve important roles in normal hemostasis. Malignancy can result in both a deficiency or excess of VWF, leading to aberrant hemostasis with either increased bleeding or thrombotic complications, as respectively seen with acquired von Willebrand syndrome and cancer-associated venous thromboembolism. There is emerging evidence to suggest VWF also plays a role in inflammation, angiogenesis and tumor biology, and it is likely that VWF promotes tumor metastasis.

Why is Misdiagnosis of von Willebrand Disease Still Prevalent and How Can We Overcome It? A Focus on Clinical Considerations and Recommendations.

Despite von Willebrand disease (VWD) being the most common inherited bleeding disorder, its accurate diagnosis is frequently shrouded by diagnostic pitfalls. VWD is frequently under-diagnosed, over-diagnosed and misdiagnosed, leading to significant avoidable patient morbidity and health care system burden. At the heart of this dilemma lies the heterogeneity and complexity of von Willebrand factor (VWF) and associated defects, and the necessity of coalescing clinical and laboratory features to obtain an accurate diagnosis.

Identification and Analysis of Mouse Erythroid Progenitor Cells.

The most common cell type in the human body, the red blood cell or erythrocyte, has a life span of approximately 3 months. To compensate for this massive cellular requirement and short life span, the major blood producing tissues contain vast numbers of erythroid progenitor cells. Erythroid progenitors differentiate progressively from hematopoietic stem cells to committed erythroid progenitors to reticulocytes lacking a nucleus and finally to functionally mature erythrocytes in the circulation.

The iron islands: Erythroblastic islands and iron metabolism.

Background: A healthy human can produce over 1 × 10 blood cells throughout their life. This remarkable amount of biomass requires a concomitantly vast amount of iron to generate functional haemoglobin and functional erythrocytes.

Scope Of The Review: Erythroblasts form multicellular clusters with macrophages in the foetal liver, bone marrow and spleen termed erythroblastic islands.

Splenomegaly: Pathophysiological bases and therapeutic options.

The spleen is the largest immune organ in the human body and is also essential for red blood cell homeostasis and iron recycling. An average human spleen is approximately 10 centimetres in length and weighs 150g. Pathological conditions can result in the spleen weighing in excess of 2000g and extending over 30 centrimetres in length.

Making Blood: The Haematopoietic Niche throughout Ontogeny.

Approximately one-quarter of all cells in the adult human body are blood cells. The haematopoietic system is therefore massive in scale and requires exquisite regulation to be maintained under homeostatic conditions. It must also be able to respond when needed, such as during infection or following blood loss, to produce more blood cells.

Ethnic disparities in causes of death among diabetes patients in the Waikato region of New Zealand.

Aim: Assist health service planning by: (1) estimating the causes and disparities in mortality among people with diabetes in Waikato and (2) examining the differences in recording of diabetes.

Method: A retrospective cohort study of diabetes patients registered with the Waikato Regional Diabetes Service. Deaths from 2003-2007 were identified among patients diagnosed with diabetes before 2003.