Relation of p53 Protein Overexpression to Subtypes of Acute Erythroleukemia

Park, Tae Hee; Park, Tae Sung; Oh, Seung Hwan; Kim, Hyung Hoi; Lee, Eun Yup; Chung, Joo Seop; Kim, Myeong You; Lee, Jeong Nyeo; Kim, Kyeong Hee; Han, Jin Yeong

Abstract

BACKGROUND
Acute erythroleukemia (AEL), FAB-M6 is a rare heterogenous disorder diagnosed by myeloblasts more than 30% of nonerythroid cells (NEC). Pure erythroleukemia (Di Guglielmo disease) with an excess of proerythroblasts can be classified as MDS or M0. An aberration of the p53 gene in acute myelogenous leukemia is rare, but related to complex karyotypes with poor prognosis.
METHODS
To evaluate heterogenous features, 32 cases of AEL or suspicious AEL were categorized as consisting of more than 50% erythroblasts and M6a with more than 30% myeloblasts of NEC, M6b with more than 30% proerythroblasts of all erythroblasts, and M6c with more than 30% both myeloblasts and proerythroblasts. The relation of the p53 protein overexpression and chromosomal abnormalities to AEL and these subtypes was investigated.
RESULTS
There were 18 M6a, 6 M6b, and 8 M6c. The percentage of erythroblasts was M6a 58.7%, 77.7% M6b, and 67.2% M6c. The percentage of myeloblasts in NEC was M6a 53.6%, M6b 4.3%, and M6c 39.2%. The percentage of proerythroblasts in all erythroblasts was M6a 5.6%, M6b 56.2%, and M6c 34.1%. Survivals of M6b and M6c were significantly shorter than M6a (12.0 vs. 2.0 vs. 2.0 months, P=0.003). Five of 11 cases showed complex karyotypes (1 M6a, 2 M6b, 2 M6c), of -5, 5q-, -7, 7q-, -17 and/or 17p-, with shorter survival and poor response. The p53 protein overexpression was M6a 27.3%, M6b 100%, and M6c 83.3%. The p53 protein overexpression was positive in all 5 cases of multiple complex karyotype with frequent treatment failure or shorter survival, but was negative in 5 normal karyotypes. CONCLUSTIONS: The occurrence of complex karyotypes and aberration of the p53 gene frequently observed in M6b and M6c subtypes of acute erythroleukemia would be considered in establishing a new and innovative treatment to target neoplastic proerythroblasts that are resistant to standard therapy for acute myelogenous leukemia.