Is Acute Erythroid Leukemia a Transitional Stage from MDS to AML?: A Study by Fluorescence in Situ Hybridization and Cytogenetics
Authors: Hwang Sang Mee , Lee Sang-ho , Kang Seong_Ho , Park Seonyang , Yoon Sung-Soo , Kim Byoung Kook , Kim Hyun Kyung , Cho Han Ik , Lee Dong Soon 
Published: April 2020

Abstract
Background: Chromosomal abnormalities of acute erythroid leukemia (AEL) are reported to be complex and nonspecific. We compared the cytogenetic abnormalities of AEL to other subtypes of acute myeloid leukemia (AML) by G- band karyotyping and fluorescence in situ hybridization (FISH) techinique using 18 probes.
Methods: 384 patients diagnosed with AML between January 2000 and December 2007 were classified morphologically by French-American-British classification. G-band karyotyping and FISH for 4 recurrent chromosomal abnormalities in AML [AML/ETO rearrangement, PML/RARa rearrangement, MLL rearrangement, inv(16)] were performed. To verify whether common cytogenetic abnormalities of myelodysplastic syndrome (MDS) were present in AEL, FISH for 5q deletion, 7q deletion, trisomy 8 and gain of 1q were performed on bone marrow nucleated cells of 25 patients with AEL. To evaluate the numerical chromosomal changes, ten additional FISH tests were done. Chromosomal enumeration probes (CEP) were primarily used and in case where there were no CEP available, probes for chromosomal rearrangement were surrogately used.
Results: Incidence of recurrent genetic changes of AML [AML/ETO, PML/RARA, MLL, inv(16)] was 0% in AEL, while the incidence of AML/ETO, PML/RARA, MLL and inv(16) rearrangement in AML excluding AEL was 12.8%, 12.7%, 5.0%, 4.6%, respectively. Frequencies of numerical chromosomal changes were 11.8% in AML excluding AEL and 44% in AEL, showing significantly higher incidence of numerical changes in AEL. Frequencies of cytogenetic changes, which are common in MDS, were 20% for 5q deletion, 32% for trisomy 8, 16% for 1q gain among AEL patients. In total, 40% of the AEL patients showed similar chromosomal changes to MDS. By G-banding, 32% of the AEL patients showed numerical change of chromosome 8 and 20% for chromosome 5. However, numerical chromosomal changes by G-banding were not statistically different between AEL and other AML, while &gt;3 complex chromosomal changes were significantly higher in AEL. (P=0.001) Out of 25 AEL patients, 4 patients (16%) were transformed from MDS and 1 patient (4%) transformed to other subtype of AML during treatment.
Discussions: Numerical chromosomal change was the most predominant genetic change of AEL, while recurrent genetic changes of AML were not found in AEL. Instead, AEL patients showed similar chromosomal changes to MDS. This implies that AEL subtype of AML is rather a separate disease entity from the other types of AML, more within the spectrum of MDS. We infer that AEL is a transitional stage from MDS to AML.
Table 1. General aspects and the summary of the results of AML and AEL*
Characteristics AML AEL Abbreviations: AML, Acute myeloid leukemia; FAB, French-American-British classification; AEL, acute erythroid leukemia * AEL diagnosed by WHO criteria ¢” FISH was done on available specimen only ¢Ô Ploidy changes were determined by 18 kinds of probes in AEL, and 4 kinds of Probes in AML subtypes excluding AEL Gender female 161 41.9% 6 22.2% male 223 58.1% 21 77.8% total 384 100.0% 27 100.0% FAB classification M0 16 4.2% M1 43 11.2% M2 124 32.3% M3 43 11.2% M4 81 21.2% M5 17 4.4% M6 27 7.0% M7 7 1.8% undetermined 26 6.8% AML excluding AEL AEL Age, years (median) 15–77 (51) 17–84 (60) &lt;60 248 69.5% 11 40.7% °Ã60 109 30.5% 16 59.3% Recurrent genetic abnormalities ¢” PML/RARA 43/338 12.7% 0/27 0.0% AML/ETO 42/327 12.8% 0/27 0.0% inv(16) 12/259 4.6% 0/27 0.0% MLL 16/319 5.0% 0/27 0.0% Abnormal karyotype 85/356 23.9% 13/27 48.1% Ploidy change by FISH ¢Ô 41/348 11.8% 14/25 56.0%