Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency.

Most eukaryotic cell types use a common program to regulate the process of cell division. During mitosis, successful partitioning of the genetic material depends on spatially coordinated chromosome movement and cell cleavage. Here we characterize a zebrafish mutant, retsina (ret), that exhibits an erythroid-specific defect in cell division with marked dyserythropoiesis similar to human congenital dyserythropoietic anemia. Erythroblasts from ret fish show binuclearity and undergo apoptosis due to a failure in the completion of chromosome segregation and cytokinesis. Through positional cloning, we show that the ret mutation is in a gene (slc4a1) encoding the anion exchanger 1 (also called band 3 and AE1), an erythroid-specific cytoskeletal protein. We further show an association between deficiency in Slc4a1 and mitotic defects in the mouse. Rescue experiments in ret zebrafish embryos expressing transgenic slc4a1 with a variety of mutations show that the requirement for band 3 in normal erythroid mitosis is mediated through its protein 4.1R-binding domains. Our report establishes an evolutionarily conserved role for band 3 in erythroid-specific cell division and illustrates the concept of cell-specific adaptation for mitosis.

Pathology Consultation on Gene Mutations in Acute Myeloid Leukemia.

OBJECTIVES: Acute myeloid leukemia (AML) is a rapidly fatal disease without the use of aggressive chemotherapy regimens. Cytogenetic and molecular studies are commonly used to classify types of AML based on prognosis, as well as to determine therapeutic regimens. METHODS: Although there are several AML classifications determined by particular translocations, cytogenetically normal AML represents a molecularly, as well as clinically, heterogeneous group of diseases. Laboratory evaluation of AML will become increasingly important as new mutations with both prognostic and therapeutic implications are being recognized. Moreover, because many patients with AML are being treated more effectively, these mutations may become increasingly useful as markers of minimal residual disease, which can be interpreted in an individualized approach. RESULTS: Current laboratory studies of gene mutations in AML include analysis of NPM1, FLT3, CEBPA, and KIT. In addition to these genes, many other genes are emerging as potentially useful in determining patients' prognosis, therapy, and disease course. CONCLUSIONS: This article briefly reviews the current most clinically relevant gene mutations and their clinical and immunophenotypic features, prognostic information, and methods used for detection.

Pathology resident and fellow education in a time of disruptive technologies.

The development of disruptive technologies is changing the practice of pathology. Their implementation challenges traditional educational paradigms. Training programs must adapt to these heuristic needs. The dual explosion of new medical knowledge and innovative methodologies adds new practice aspects to the pathologist's areas of expertise. This transformation potentially challenges the traditional core model of training. It raises questions as to how pathology should incorporate future expanding subspecialty needs into educational and practice models. This article examines the impact of these disruptive technologies on resident and fellow education and explores alternative educational and practice models that may better accommodate pathology's future.