Immunological and cytochemical characterization of megakaryocytic lineage leukemia.

Morphology alone, even at the ultrastructural level is insufficient for identification of PMKB. With LM cytochemistry, no specific enzymes can be demonstrated in human PMKB. PPO, which is distinct from granulocytic peroxidases, is present in the ER of platelets, MK and PMKB. Thus, for several years, PPO detection has constituted the only marker for the reliable diagnosis of AMKL. However PPO detection requires EM studies which may present difficulties for routine diagnosis. The limitation of this cytochemical method results from the fact that other heme enzymes are also detected in ER from several non-MK cells when appropriate and sensitive cytochemical methods are used. In addition, partial PPO deficiency can be detected in AMKL. The establishment of a large panel of monoclonal and polyclonal antibodies against platelet proteins present either on the membrane or within alpha-granules has permitted determination of the phenotype of normal PMKB which differentiate from CFU-MK in the early days of in vitro culture. The immunologic phenotypes of leukemic PMKB are identical to those of their normal counterparts but their maturation is blocked at different levels corresponding to three main different phenotypes; PPO is expressed in all phenotypes. The most immature or PMKB I is HLA-DR+, 80 H 5 or MY 9+ (myeloid-lineage antigens also expressed on stem cells); PMKB II lack this labeling but acquire platelet Gp IIb, IIIa while GpIb identified by monoclonal antibody AN 51 is absent or weak. PMKB III which represent the more frequent phenotype express all Gp and exhibit diffuse cytoplasmic labeling for vWF, PF4, TPS, fibrinogen, in the absence of alpha-granules at EM level. Changes in the phenotype (from III and II to I) can be observed during the evolution of the same patient. In spite of a partial PPO deficiency in blasts and platelets from several cases of AMKL, PPO appears to be the earliest and most sensitive marker.