Introduction

Article Outline

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This issue is the second part of the two issues on bone marrow disorders. As mentioned in the Introduction to Part I (Bone Marrow Disorders: Recent Advances, Part I), a lot of hard work and many hours of discussion have preceded the publication of the WHO series of classifications of human neoplasms. However, advances in our understanding of molecular events that are characteristic of, precede, or define a disease or disease group have nowhere else had such a profound impact on disease classification as in the WHO classification of tumors of the hematopoietic and lymphoid tissues. In the case of the myeloid neoplasms, the classification has categorized some entities, e.g. acute myeloid leukemia, into different types based not only on their morphology, but also on molecular genetic and somewhat surprisingly, on clinical criteria. In addition, it has utilized various molecular events that result in the dysregulation of tyrosine kinase cell signaling pathways to allow the categorization of seemingly diverse myeloproliferative neoplasms into related families of diseases.

In the past 2 to 3 years, since the publication of the WHO classification in 2008, dynamic progress in the array technologies and next-generation amplicon deep sequencing has provided new insights into the molecular pathogenesis of myeloid neoplasms and identification of new mutations and genetic alterations. Although detailed molecular characterization of these mutations in a clinical setting is difficult, at least at this time, they provide important insights into the molecular pathogenesis and biology of this group of diseases and provide information for potential therapeutic targets. This information may ultimately lead, in the future to a new refined classification of this group of neoplasm.

In these exciting times when advances in technology enable the rapid accumulation of very large amounts of biological information, possibly best illustrated by the fact that sequencing of the full human genome can be obtained for about $6,000 in one week, the odds are that we will see major insights into the biology of tumors of hematopoietic tissues in the foreseeable future. Seminars in Diagnostic Pathology has dedicated two of its issues, May 2011 and August 2011, to malignant lymphomas with the aim to present future perspectives, after the fourth edition of the WHO Classification was released in 2008. This issue and an upcoming issue (February 2012), attempt to summarize current concepts in the diagnosis of bone marrow disorders and recent advances in this field, after the 2008 WHO Classification.

In hematopathology, the diagnostic process has always been one which simulates interesting detective work, of putting together a jig saw puzzle of several apparently diverse pieces of information derived from various sources, with a final diagnosis emerging only after the last piece is in place. This said, we all know that for many biological entities we are still missing many pieces of the puzzle and that it is entirely possible, if not guaranteed, that future discoveries will show us clearly new pictures emerging from a somewhat imperfect current understanding of bone marrow disorders and to what degree our current classification is still “out of focus” or at least in need of “fine tuning”.

Myelodysplastic syndrome, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1 are included in Part I (Bone Marrow Disorders: Recent Advances, Part I), while mastocytosis and acute leukemias are included in the February 2012 issue (Bone Marrow Disorders: Recent Advances, Part II). These reviews not only provide a concise insight into recent advances, but also further highlight the concepts and logic behind the 2008 WHO Classification, and ongoing discussions. Part 2 also has a review on the pathological lesions associated with Sickle Cell anemia.