Background: Acute erythroid leukemia (AEL) or AML-M6 predominantly affects older adults and is rare in childhood. Compared with other AML subtypes, AEL remains relatively understudied because of its rarity. We established LS-CHM, a novel AEL cell line derived from the ascitic fluid of a patient with congenital leukemia. Interestingly, leukemic cells persisted in the ascitic fluid even after successful eradication from the bone marrow and extramedullary sites. Method: Leukemia cells from the ascites fluid exhibited robust proliferation in culture independent of cytokine requirement and were further characterized by flow cytometric immunophenotyping, cytogenetics, cell cycle and doubling time analysis, colony formation, genome and RNA sequencing, myeloid gene next generation sequencing, and cytotoxicity analysis. Results: LS-CHM displayed CD36, partial CD235a, CD31, CD43, and CD71 expression and demonstrated in vitro robust growth and high sensitivity to chemotherapeutic agents. A PDX mouse model showed development of leukemia. Genomic analysis revealed a frameshift BCOR mutation in the absence of additional mutations and downregulated TP53 expression with an exonic non-deleterious mutation. RNA sequencing of LS-CHM cells revealed upregulation of two cohesin complex genes, RAD21 and SMC3, whose high levels are associated with hematopoietic stem cell differentiation into erythroid lineage. Conclusions: LS-CHM represents the first congenital AEL-derived cell line, in contrast to the predominantly adult-origin and often secondary erythroid leukemia cell lines available currently. Thus, LS-CHM provides a unique pediatric and extramedullary AEL model, expanding the existing spectrum of AEL cell lines and offering valuable opportunities for biologic and therapeutic investigations.