Multidrug resistance: focus in hematology

The appearance of chemoresistance is the most relevant limitation of chemotherapy. It has been shown that multidrug resistance (MDR) is frequently related to the expression of a membrane glycoprotein (P-170). This protein is able to bind ATP and leads to decreased accumulation of structurally unrelated antineoplastic drugs extensively used in the management of hematological patients. The availability of monoclonal antibodies and probes allowed extensive studies both "in vitro" and "in vivo" of the protein structure and of its mechanism of action. The P 170 activity may be antagonized by drugs able to compete with chemotherapic agents for the binding or by calcium antagonists that inhibit the expulsion activity of the protein. P 170 has been found in variable percentages of several hematological malignancies such as leukemia, myelodysplastic syndromes, myeloma and lymphoma. The reported data seem to indicate that the patients carrying P 170-positive neoplastic cells should be treated with drugs that are not bound by the protein. However, the possibility of inhibiting the protein function and the recent reports suggesting the use of P 170 as a target for immunotoxins could be the basis for new therapeutic protocols.     

Challenging gold standard hematology diagnostics through the introduction of whole genome sequencing and artificial intelligence

The diagnosis of hematological malignancies is rather complex and requires the application of a plethora of different assays, techniques and methodologies. Some of the methods, like cytomorphology, have been in use for decades, while other methods, such as next-generation sequencing or even whole genome sequencing (WGS), are relatively new. The application of the methods and the evaluation of the results require distinct skills and knowledge and place different demands on the practitioner. However, even with experienced hematologists, diagnostic ambiguity remains a regular occurrence and the comprehensive analysis of high-dimensional WGS data soon exceeds any human's capacity. Hence, in order to reduce inter-observer variability and to improve the timeliness and accuracy of diagnoses, machine learning based approaches have been developed to assist in the decision making process. Moreover, to achieve the goal of precision oncology, comprehensive genomic profiling is increasingly being incorporated into routine standard of care.     

Historical hematology: May-Hegglin anomaly

May-Hegglin anomaly is a rare autosomal dominant platelet disorder characterized by thrombocytopenia, giant platelets, and unique leukocyte inclusion bodies. This disorder was first described by May, a German physician, in 1909, and was subsequently described by a Swiss physician, Hegglin, in 1945. The pathogenesis of the disorder had been unknown until recently, when mutations in the gene encoding for nonmuscle myosin heavy chain IIA (MYH9) were identified. Unique cytoplasmic inclusion bodies are aggregates of nonmuscle myosin heavy chain IIA, and are only present in granulocytes. It is not yet known why inclusion bodies are not present in platelets, monocytes, and lymphocytes, or how giant platelets are formed. Interestingly, MYH9 is also found to be responsible for several related disorders with macrothrombocytopenia and leukocytes inclusion, including Sebastian, Fechtner, and Epstein syndromes, which feature deafness, nephritis, and/or cataract. Current interest is centered upon the mechanisms by which a single mutation causes a variety of phenotypes.     

Introduction: molecular diagnostics in hematology.

Advances in molecular biology of the last 30 tears have transformed the field of hematology. Molecular analysis has clarified the pathogenesis of a host of hematologic disorders, including hemoglobinopathies, coagulation disorders, hypercoaguable states, and hematologic malignancies. This volume is aimed at bringing these compelling advances in molecular biology research to the bedside. Through progress in the molecular understanding of hematology, great strides have been made in our ability to diagnose and treat patients with hematologic disease. These advances in turn have given rise to more questions that will guide future studies of the biology of hematopoietic abnormalities and continue the exciting interaction of basic science and clinical medicine.     

Invasive fungal infections in hematology: new trends

Invasive fungal infections (IFI) are among the most feared complications of patients being treated for a hematological malignancy. Currently, most serious IFI occur in patients with acute leukemia and after allogeneic hematopoietic stem cell transplantation. Although Candida albicans and Aspergillusspp. continue to be the main pathogens, the proportion of patients infected by non-albicans species of Candida and other yeasts and by other filamentous fungi is rising in most institutions. Risk factors for the various IFI differ, and it is thus of utmost importance to realize that not all patients are the same with respect to the risk for developing the various IFI. Recent advances in diagnosis now allow the use of very sensitive imaging techniques with an extremely low negative predictive value. Among the novel microbiologic methods, the galactomannan antigen test is now commercially available for routine use in the diagnosis of aspergillosis, while DNA fungal detection is still experimental. For the first time, clinicians now have a broad range of antifungals to chose from, with special emphasis on amphotericin B preparations, novel broad-spectrum azoles, and the echinocandins. However, the exact place of these agents in treating different IFI will need to be found in the near future.     

Microarrays in hematology.

Microarrays are fast becoming routine tools for the high-throughput analysis of gene expression in a wide range of biologic systems, including hematology. Although a number of approaches can be taken when implementing microarray-based studies, all are capable of providing important insights into biologic function. Although some technical issues have not been resolved, microarrays will continue to make a significant impact on hematologically important research.