Gene abnormalities responsible for familial
Pelger-Huet anomaly have been recently discovered. Abnormalities in sequence of
Lamin B Receptor(LBR) gene results in a lack of LBR
protein that is essential for
chromatin-binding to nuclear membrane. In neutrophils lacking LBR
protein shows abnormal bilobular or monolobular nuclear forms and hyper-condensed
chromatin-aggregation. We re-analyzed distribution of such
Pelger-Huet anomaly in other cell lineages; we found that not only neutrophils but erythroblasts, monocytes, lymphocytes, plasma cells, eosinophils and basophils are also carrying
chromatin-hypercondensation. One third of megakaryocytes are also binucleated like neutrophils. We compared neutrophil morphology between familial
Pelger-Huet anomaly and so called
pseudo-Pelger-Huet anomaly observed in patients with
myelodysplastic syndromes(MDS) and
acute myeloid leukemia(AML). The neutrophils in MDS were much similar to those of the familial anomaly, but neutrophils of AML, such as t (8;21) M2-AML and t (15;17) M3-AML, showed more heterogeneous pattern in lobulation and
chromatin-hypercondensation. Especially in M3, differentiation-induction by
all-trans retinoic acid induced a marked neutrophilia with
pseudo-Pelger-Huet anomaly without
chromatin-hypercondensation. Lack of LBR
protein in familial
Pelger-Huet anomaly results in hypolobulation and
chromatin-hypercondensation in neutrophils, but in other cells such as erythroblasts and lymphocytes only
chromatin-hypercondensation can be observed. In contrast
pseudo-Pelger-Huet anomaly are more heterogeneous in morphology compared to the familial anomaly. The lack of leukemic or MDS transformation in the familial anomaly is a sharp contrast to the neoplastic nature of the
pseudo-Pelger-Huet anomaly. In conclusion, our morphological recognition of certain abnormality of cells shows an marked progression when genetic abnormality responsible for some of them are discovered, and often make us recognize a further heterogeneity in them. We, hematologists and technicians, must be well prepared to report our own observation of an un-explained morphological abnormality.