Page 237 - Haematologica Vol. 107 - September 2022

LETTER TO THE EDITOR
sessment of p53 using immunohistochemistry can be chal- lenging, especially in cases where PEL is mixed with residual normal hematopoietic cells in the background which have a wild-type p53 staining pattern.
Lastly, we suggest that the category of PEL should be pre- served, despite the fact that some cases also can be clas- sified as therapy-related AML/MDS or AML with myelodysplasia-related changes (AML-MRC) using the cur- rent World Health Organization (WHO) criteria. We believe classifying these cases as something other than PEL does not fully capture the distinctive features of this disease. The rationale for this proposal includes: i) PEL cases, irrespec- tive of their origin (de novo or secondary), share similar clini- copathological features including poor response to treatment, dismal prognosis, complex karyotype, and bial- lelic TP53 alterations. By contrast, the WHO-defined cat- egories of therapy-related AML/MDS or AML-MRC are highly heterogeneous at the molecular level, and are associated with highly variable prognoses for different patient sub- sets.12,13 We believe that the distinctive clinicopathologic and molecular features of PEL may be obscured when these neoplasms are placed in the therapy-related AML/MDS or AML-MRC WHO categories; ii) the survival of PEL patients with a history of receiving cytotoxic therapy or MDS is simi- lar to de novo PEL patients but is worse than patients with therapy-related AML12 and AML-MRC,13 respectively; iii) all PEL cases, whether they are de novo or secondary, share distinctive morphologic features with prominent pronormo- blast proliferation. Pronormoblasts have been shown to play an important role in treatment resistance and increased pronormoblasts have contributed to a poorer prognosis in AML patients.14,15 By keeping secondary PEL cases in the cat- egory of PEL, these cases can be studied together to ex- plore therapeutic strategies targeting the neoplastic pronormoblasts. Of note, the number of de novo PEL cases in our study is relatively small and future studies to include more cases will be valuable.
In summary, we show that PEL is characterized by biallelic TP53 loss-of-function, a complex karyotype, poor response to AML or MDS directed therapy, and a very dismal progno- sis. These unique features are the same for de novo or sec- ondary cases of PEL, and therefore we advocate for keeping them under the entity of PEL to facilitate further studies and drug discovery. Immunohistochemistry for p53 can be used as a preliminary screening tool to assess TP53; strong p53 expression correlates with missense mutations of TP53 and a null p53 pattern is often associated with frameshift, nonsense, or TP53 mutations involving splice sites.
References
1. Wang W, Wang SA, Medeiros LJ, Khoury JD. Pure erythroid leukemia. Am J Hematol. 2017;92(3):292-296.
Authors
Hong Fang,1 Sa A. Wang,1 Joseph D. Khoury,1 Siba El Hussein,1 Do Hwan Kim,1 Mehrnoosh Tashakori,1 Zhenya Tang,1 Shaoying Li,1 Zhihong Hu,2 Fatima Zahra Jelloul,1 Keyur P. Patel,1 Timothy J. McDonnell,1 Tapan Kadia,3 L. Jeffrey Medeiros1 and Wei Wang1
1Department of Hematopathology, The University of Texas MD Anderson Cancer Center; 2Department of Pathology, The University of Texas Health Science Center at Houston and 3Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Correspondence:
W. WANG - wwang13@mdanderson.org
https://doi.org/10.3324/haematol.2021.280487
Received: December 16, 2021. Accepted: April 28, 2022. Prepublished: May 5, 2022.
©2022 Ferrata Storti Foundation Published under a CC BY-NC license
Disclosures
No conflicts of interest to disclose.
Contributions
HF had substantial contributions to the design of the work, drafting the work, revising it, and the acquisition, analysis, interpretation of data for the work. WW had substantial contributions to the conception and design of the work, revising it critically for important intellectual content, and analysis, interpretation of data for the work. SAW and LJM had substantial contributions to the conception and design of the work and revising it critically for important intellectual content. JDK, SE, DHK, MT, ZT, SL, ZH, FZJ, KPP, TJM, and TK had contributions to the acquisition, analysis of data for the work and revising it critically for important intellectual content. All authors had final approval of the version to be published and an agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Data-sharing statement
All data are available for sharing upon request to the corresponding author.
2. Reinig EF, Greipp PT, Chiu A, Howard MT, Reichard KK. De novo pure erythroid leukemia: refining the clinicopathologic and
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