Submitting Author: Boncher, Julia Jiyoon, MD
Institution: Cleveland Clinic
Additional authors:James R Cook, MD, PhD
Session: B Lymphoblastic Leukemia/Lymphoma

The patient is a 41 year old woman who was diagnosed at an outside institution with Philadelphia-chromosome positive B acute lymphoblastic leukemia (Ph+ B-ALL) with CNS involvement. She received induction chemotherapy with HyperCVAD, dasatinib and intrathecal chemotherapy. She initially achieved a complete morphologic and cytogenetic remission, but peripheral blood RT-PCR studies remained positive for BCR/ABL transcripts. Approximately one year after induction, peripheral blood examination revealed 22% blasts, consistent with recurrent disease. A bone marrow biopsy was performed at our institution to confirm relapsed ALL.

The bone marrow aspirate demonstrated 67% blasts. The core biopsy was hypercellular (>90%) with sheets of immature mononuclear cells consistent with blasts.

Flow cytometric studies demonstrate a lymphoid blast population expressing CD19, CD10, CD13, dim CD20, CD33, CD34, HLA-DR and TdT. The blasts were negative for cytoplasmic and surface IgM.

Metaphase cytogenetic studies demonstrated an abnormal karyotype: 46,XX,t(3;11)(q13;p11.2),t(9;22)(q34;q11.2)[13]/46,XX[8].

RT-PCR studies were positive for p190 BCR/ABL transcripts.

FISH studies were positive for a BCR/ABL translocation.

SNP array karyotyping (Affymetrix CytoScan HD) demonstrated abnormal findings including a 40kb deletion of 7p12.2 involving IKZF1 (Ikaros) exons 6-12, a 560 kb deletion involving the entire EBF1 gene on 5q33.3, and a 3.42 MB deletion of 9p13.3-9p13.2 that includes the PAX5 gene.

This case illustrates the use of SNP microarray karyotyping studies to detect several recurrent deletions associated with B-ALL. In particular, deletions of the IKZF1 (Ikaros) gene are identified in 70-80% of Ph+ ALL and in a smaller proportion of high risk B-ALL lacking BCR/ABL. Deletions of IKZF1 are associated with a poor prognosis, both in Ph+ and Ph- ALL. Deletions of PAX5 and EBF1 are also recurrent abnormalities in ALL. Several techniques have been utilized to detect these recurrent deletions in ALL including multiplexed PCR, multiplex ligation dependent probe amplification (MLPA), and FISH. This case illustrates the ability of SNP array karyotyping to screen for such copy number changes across the genome.

Recurrent Philadelphia-chromosome positive B acute lymphoblastic leukemia, with IKZF1, EBF1, and PAX5 deletion.

Recurrent Philadelphia-chromosome positive B-acute lymphoblastic leukemia, with IKZF1, EBF1, and PAX5 deletion

Case 210