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18. Concomitant presence of iAMP21 and ETV6-RUNX1 / BCR-ABL1 in childhood B-cell Acute Lymphoblastic Leukemia

      Intrachromosomal amplification of chromosome 21 (iAMP21) is a high-risk chromosomal abnormality reported in 2% of pediatric patients with precursor B-cell acute lymphoblastic leukemia (B-ALL). Although it is frequently accompanied by a complex karyotype, coexistence of iAMP21 with other primary cytogenetic abnormalities in B-ALL, such as t(12;21)(p13;q22)/ETV6-RUNX1 and t(9;22)(q34;q11.2)/BCR-ABL1, is very rare. The attributes of cooperating aberrations and the leukemogenesis of iAMP21 are not well elucidated. Herein, we describe three pediatric B-ALL patients with concomitant presence of iAMP21 and either ETV6/RUNX1 or BCR/ABL1 rearrangements. Chromosome and FISH analyses for patient 1 showed higher percentage of t(12;21) accompanied by iAMP21 in a subset of cells, suggesting the iAMP21 could act as a second hit aberration. This patient had relapsed disease three years after diagnosis and a second relapse two months after bone marrow transplantation that displayed new chromosomal abnormalities in addition to the ETV6-RUNX1 fusion and iAMP21. Patient 2 and patient 3 had abnormal cytogenetic results including iAMP21 in conjunction with t(9;22). These two anomalies were found in the same clone by karyotyping analysis. However, based on the percentages of iAMP21 and t(9;22) in FISH studies, iAMP21 was considered as the primary abnormality. Patient 2 had a relapse one year after diagnosis with persistence of the iAMP21 and new karyotypic abnormalities, but in the absence of t(9;22). Although patient 3 achieved MRD negativity at the end of induction as determined by flow cytometry, she developed septic shock and passed away during consolidation. Our data support the poor prognostic impact of iAMP21 and further demonstrate the varying pathogenic role of iAMP21 when coexisting with different cytogenetic lesions in B-ALL. More cases are needed for further delineation of the clinical significance of concomitant primary cytogenetic abnormalities in B-ALL to improve treatment decision making.
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