Page 236 - Haematologica Vol. 107 - September 2022

LETTER TO THE EDITOR
critical role in the development of PEL. Of note, biallelic TP53 alteration is not specific to PEL and can be seen in other myeloid neoplasms, such as AML8 and therapy-re- lated MDS.9 Thus, TP53 mutations alone may not be suf- ficient to block the differentiation of erythroid lineage and drive pronormoblast proliferation, a pathognomonic fea- ture of PEL. Alterations of other genes (not covered in our mutation panels) or pathways involved in erythroid differ- entiation likely also play a role in PEL development.
As mutational analysis often takes time, checking p53 ex- pression status by immunohistochemistry has been used
as a surrogate to predict the presence of TP53 muta- tions.6,10,11 One caveat is that TP53 mutations do not always correlate with p53 overexpression. In the current study, approximately one quarter of PEL cases showed a null pattern by immunohistochemistry. In these cases, TP53 mutations were either frameshift, nonsense, or involved a splice site. Of note, the null pattern of p53 expression can usually be distinguished from the “negative” wild-type pattern which often shows variable p53 expression in a subset of cells and the staining intensity ranges from weak to moderate (Figure 1C). In some cases, however, as-
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B
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Figure 1. The expression pattern of p53 by immunohistochemistry in pure erythroid leukemia. Immunohistochemistry shows two patterns of p53 expression: complete absence of p53 expression (case #1, upper panel) and uniform and strong overexpression (case #17, middle panel). Of note, in the case with absence of p53 expression in tumor cells (case #1, upper panel), there were scattered reactive cells in the background variably positive for p53, serving as positive controls. A normal bone marrow and its p53 expression by immunohistochemistry is illustrated in the lower panel, in which p53 is variably expressed in a subset of cells with weak to moderate intensity.
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