Myeloproliferative Disorders: Biology and Management PDF

Preface

What an exciting age for those of us interested in the myeloproliferative diseases!

Myeloproliferative diseases-a term first used 55 years ago by the famous hematologist William Dameshek-include chronic myeloid leukemia, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). These are clonal hematopoietic stem cell disorders characterized by the expansion of one or more cell lines accompanied by varying degrees of marrow fibrosis.

Slumbering in the diagnostic and therapeutic advances of other areas of hematology, explosive interest in them beganwith the exploitation of the molecular understanding of chronic myeloid leukemia and by the development of the small molecule, imatinib. This drug not only revolutionized the treatment of chronic myeloid leukemia, but also stimulated interest in the Philadelphia-chromosome– negative (Ph⁻) myeloproliferative diseases because of their clinical and hematologic similarities. The Ph-negative diseases nevertheless remained in relative hematologic limbo until the discovery of a molecular abnormality now found in all patients with polycythemia vera and in about half the patients with essential thrombocythemia and primary myelofibrosis. This abnormality, found in the regulatory domain of JAK2, is denoted as JAK2^V617F.

In addition to the intellectual appreciation of the biologic relevance of the Ph-negative diseases, are these diseases appropriate to study with intensity, owing to their relative infrequency? The answer is an unequivocal "yes." The model of BCR-ABL/imatinib has provided enthusiastic impetus for understanding the mechanisms of action of JAK2^V617F and for developing drugs effective against this abnormality. This has applicability not only for the more common Ph-negative MPDs, PV, ET, and PMF, but also for the less common ones, mast cell disease and the hypereosinophilic syndromes. This textbook has been prepared both for the more casual student of the MPDs as well as for those of us who are particularly interested in these disorders. We have also selected topics of interest to the clinician treating these patients and to laboratory scientists studying the molecular and cytogenetic abnormalities of these illnesses. As our understanding unfolds, specific inhibitors of the JAK2 pathway may be discovered, which are uniquely useful in the clinic. Until that time, more traditional treatments, which are reviewed, such as phlebotomy, anagrelide, hydroxyurea, interferon, and marrow transplantation, will continue to be employed in a rational manner, acknowledging the limitations of our current therapeutics.

We are very grateful to our contributors for their scholarly and timely contributions that have made this volume possible. This is particularly important because of the rapid advances that are currently being made. Hopefully, this book will serve as a repository and summary of recent information relevant to the field.