Chronic Myeloproliferative Disorders PDF

Preface

Claims of priority can almost always be challenged but it is generally agreed that John Hughes Bennett in Edinburgh and Rudolph Virchow in Berlin were the first to publish accurate case reports of what must surely have been chronic myeloid leukaemia. Both published in 1845 and probably neither was aware of the other's publication until later. In 1879 a German surgeon, Gustav Heuck, described two young patients with massive splenomegaly and abnormal leukocytes and nucleated red cells in the blood – a condition we would accept today as primary myelofi - brosis. Louis Vaquez can legitimately claim credit for the fi rst description of polycythemia vera in 1892, though of course the disease was for many years known as Osler-Vaquez disease in recognition of Osler's description in 1903 of four cases of what today we accept as polycythemia vera. Epstein and Goedel were the first to describe the condition known to as essential thrombocythemia. These four conditions were generally regarded as distinct though various haematologists in the fi rst half of the 20th century had noted trilineage involvement in each. In the editorial he wrote in Blood in 1951 William Dameshek's contribution unquestionably was to group these three disorders together with others under the general heading of myeloproliferative disorders and to draw attention to their common features. He did not specifi cally refer to essential thrombocythemia.

"....To put together such apparently dissimilar diseases as chronic granulocytic leukemia, polycythemia, myeloid metaplasia and diGuglielmos's syndrome may conceivably be without foundation, but for the moment at least, this may prove useful and even productive. What more can one ask of a theory?" (Dameshek, 1951)

He speculated that they might all be due to some ill-defined exogenous factor stimulating excessive haemopoiesis but of course the emphasis has shifted in recent years to the notion that molecular defects acquired in single haemopoietic stem cells may be the primary cause of these different but related disorders. This then is the justification for attempting to cover in a single book the various chronic myeloproliferative disorders. The only major distinction that we have adopted, conveniently but perhaps somewhat artificially, is to divide them into Ph-positive and Phnegative MPDs, but the two categories do resemble each other almost as much as they differ individually.

If progress in understanding the biology of the MPDs was rather slow in the first half of the 20th century, the MPD student has been richly rewarded in the subsequent 60 years. Obviously important landmarks, to mention only a few, were the discovery of the Ph chromosome, the characterisation of the (9;22) translocation, the identification of the breakpoint cluster region and of the BCR-ABL fusion gene. These major developments were followed much more recently by the identification of the V617F mutation in JAK2 exon 14 and other mutations in JAK2 exon 12, which seem to play a key role in the Ph-negative MPDs. One may well ask whether this remarkable progress in understanding the molecular biology of the MPDs will presage similar advances in understanding other malignant conditions with ensuing implications for therapy - the so-called paradigm shift in the overall orientation of research. Early indications suggests that the answer may well be ‘yes'.

For this edition we have asked a number of experts to contribute individual chapters summarising the state of play for 2008. We recognize that each chapter necessarily relies heavily on published work but we believe that to bring the various topics together in one easily readable book will be a real benefit for scientists, clinical haematologists and students who are not already working in the field and do not have time to read all the original literature – at last search Google produced 12 million references to leukaemia and PubMed more than 200 000 for myeloproliferative diseases.

So we must express our thanks to the authors who all contributed their excellent chapters. Actually writing for a book of this kind always takes much longer than one imagines when one accepts the original invitation so we appreciate their efforts. We hope the reader will too.