Lineage infidelity in chronic myeloid leukemia. Demonstration and significance of hybridoid leukocytes

Blood smears from 13 cases of chronic myeloid leukemia (CML) were examined for bigranulated (basophil/eosinophil) cells. The cells were stained with May-Grünwald-Giemsa, toluidine blue, Biebrich scarlet, Adams' reaction, and were reacted for KCN-resistant peroxidase in two cases. A sequential stain (toluidine blue/Biebrich scarlet/Adams' reaction) was applied to 50 cells in each case. Hybridoid cells occurred in all cases with varying frequency. Double granulation was not only found in immature, non-segmented cells but often in mature segmented cells. The chimeric cells were difficult to detect with May-Grünwald-Giemsa. Biebrich scarlet and Adams' reaction being superior in this respect to Biebrich scarlet. Some granules that were positive by Adams' reaction did not stain with Biebrich scarlet. This is in sharp contrast to the normal and is, therefore, interpreted as a granule atypicality. Since under normal circumstances, eosinophilic and basophilic granules can be viewed as mutually exclusive markers of the respective granulocytic lineages, the simultaneous occurrence in CML cells of both markers demonstrates lineage infidelity. Until now lineage infidelity has been reported only in immature cells. However, our results show that lineage infidelity also occurs in mature segmented cells. This indicates that the progenitors of these chimeric granulocytes follow false genetic programs producing cells with profound irreversible neoplastic aberrations.