Under normal circumstances, the marrow progenitor cells respond selectively to differing but specific stimuli. Examples include the rise in white blood cell (WBC) count that occurs during a bacterial infection or the elevation of the platelet count after hemorrhage. Reactions such as these are self-limited, for the marrow reverts to its normal status once the stimulus subsides. Myeloproliferative disorders (MPDs), on the other hand, comprise a group of diseases in which pluripotent stem cells proliferate more or less en masse, at least at the onset of the illness. In the hematology literature, opinions differ as to which diseases should be included in the MPD group, but based upon improvements in clinical diagnosis and refinements in cytogenetics, and molecular biology, the diseases of major clinical importance include chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET) and agnogenic myeloid metaplasia (AMM). In general, the diagnostic difficulties associated with the MPDs relate to their clinical symmetry ("clinical mimicry") and, except for CML, the lack of clinically applicable clonal markers. Thus, they share similar clinical and hematologic features. Their origin from a multipotent hematopoietic stem cell leads to clonal dominance over normal hematopoietic progenitor cells, giving rise to increased production of one or more of the formed elements of the blood. As examples, in PV, although an increased red blood cell (RBC) mass is the sine qua non at diagnosis, such patients often have an increase in the WBC count and/or platelet count. Physical examination of a patient with an MPD often reveals an enlarged spleen and biochemical abnormalities such as elevation in the serum values of uric acid, vitamin B12, and B12-binding protein. A biochemical marker that can be of value in distinguishing one MPD from another is the concentration of leukocyte alkaline phosphatase found in the cytoplasm of neutrophils. It is typically absent in patients with CML, increased in PV and ET, and variably increased, normal, or decreased in AMM. Although cytogenetic abnormalities are seen in all patients with the MPDs, the only consistent cytogenetic abnormality, the Philadelphia (Ph) chromosome, occurs in CML, sharply distinguishing it from the others. To a varying degree, increased reticulin fibers are present in the bone marrow in all the MPDs, and as the disease progresses, fibroblastic proliferation becomes evident (probably a reactive phenomenon).

Only recently has it been appreciated that the megakaryocytes are morphologically abnormal in the myeloproliferative diseases, and biologically, are central to the genesis of the fibrosis that occurs in the marrows of patients with MPDs. An experienced hematopatholo-gist may suspect the appropriate clinical diagnosis by studying the structural characteristics of the megakary-ocytes in a bone marrow biopsy from a patient with an MPD, as their appearance differs among the four diseases.

Acute leukemia develops as an end result of all the MPDs. In decreasing order of frequency, it occurs in CML, AMM, PV, and rarely in ET.1'2 Acute leukemia may be a natural evolution of the disease, as is seen most often in CML, or it may also be related to the drugs used in treating the primary illness.12

0 0

Post a comment