77. dic(7;9):A distinct entity in B-ALL with multiple genomic aberrations including IKAROS and PAX5

dic(7;9) is a rare (<1%) and recurrent abnormality in both pediatric and adult B-ALL, resulting in partial monosomy of chromosomes 7p and 9p. Co-occurrence of dic(7;9) with PAX5 gene alterations including deletions, mutations and amplification have been reported. PAX5 encodes the B lymphoid transcription factor gene that is important in regulating B cell lineage differentiation, leading to B-cell development and may play a crucial role in B lymphoid leukemogenesis.

Here, we present two cases of pediatric B-ALL with dic(7;9) with complex genomic aberrations.

Case 1: is a four year old female who presented in 2024 with orbital and left sinus maxillary masses, anemia, fever and leukocytosis with peripheral blasts. Karyotype and fish were complex with 45,XX,der(7)dic(7;9)(p11.2;p13)del(7)(p13p11.2)t(7;20)(p13;q11.2),der(20)t(7;20)(p13;q11.2)[13]/46,XX[7]. SNP array revealed loss of 7p and 9p including IKAROS and PAX5, respectively.

Cerebral sinus fluid demonstrated a leukocytosis with leukemic blasts, resulting in a CNS3b classification. She had negative minimal residual disease at the end of induction on a very high-risk standard of care protocol and on consolidation therapy.

Case 2: is a 10 year old male referred in 2022 for a month of fever and fatigue.. karyotype was complex with several rearrangements. 45,XY,dic(7)t(7;9)(p13;p13),-9,der(10)t(9;10)(q34.1;q22),der(12)t(7;12)(p13;p13),der(13)t(10;13)(q22;q34)[11]/46,XY[9].

The patient was treated on a standard risk standard of care protocol and had negative minimal residual disease at the end of induction. He remains in remission during maintenance therapy.

Given the two dic (7;9) cases described here have complex karyotypes, it is possible that PAX5 and IKZF1 alterations may be contributing to this complex cytogenetic entity.