Acute Erythroid Leukemias Histologic, Cytogenetic and Molecular Characterization
Z Zuo, A Kasyan, P Chandra, J Medeiros, H Koeppen. University of Texas M.D. Anderson Cancer Center, Houston, TX
Background: Acute erythroid leukemias (AEL) are uncommon types of acute myeloid leukemias with markedly heterogeneous morphologic, immunophenotypic and molecular features.
Design: We reviewed the clinical, histologic, cytogenetic and molecular data of 47 patients with AEL seen at our institution. All cases strictly met the criteria outlined in the WHO classification . Molecular studies included mutational analysis for Ras, KIT and FLT3 genes.
Results: The male to female ratio was 3.7, The mean age of the patients was 56 years with a range from 18 to 84. 80% were classified as primary AEL, while the remaining cases arose in patients with an antecedent MDS. Morphologically, the bone marrow was hypercellular (mean cellularity of 73%) with mean bone marrow and peripheral blood blast counts of 45% of non-erythroid precursors and 8%, respectively. Dysplastic changes in the erythroid, megakaryocytic and granulocytic lineages were seen in 84%, 55% and 31%, respectively; ringed sideroblasts were seen in 6% of cases. Two cases fulfilled the WHO criteria of pure erythroleukemia. Karyotypic abnormalities were seen in 67% of cases; 18% demonstrated a single chromosomal abnormality and 49% showed complex changes involving two or more chromosomes. Aberrancies of chromosome 5 (33%), 7 (35%) and 11 (16%) were seen in the context of complex cytogenetic abnormalities. Trisomy 8 represented 50% of cases with a single chromosomal abnormality. Mutations of the FLT3 gene were seen in 2 of 36 patients (one internal tandem duplication, one D835 mutation). None of the cases showed mutations in the RAS or KIT genes. The average survival of patients with a diploid karyotype, a single cytogenetic abnormality or complex cytogenetic changes were 18.5, 20 and 7.6 months, respectively. Statistical analysis revealed that patients with complex cytogenetics had significantly shorter survival when compared to patients a with diploid karyotype (p=0.045) or patients with a single chromosomal abnormality (p=0.017). The two patients with pure erythroid leukemia showed survival times of 4 months and less than 12 months, respectively, complex cytogenetic abnormalities including monosomy 5 and 7 and trisomy 8 and wildtype FLT3 and RAS genes.
Conclusions: Our results demonstrate a high incidence of complex karyotypic abnormalities in AEL and a low frequency of FLT3, KIT or RAS gene mutations; the karyotypic changes are similar to those seen in MDS. Further characterization of AEL will allow a distinction from or inclusion in the appropriate categories of MDS.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 178, Wednesday Afternoon