Ashwini Yenamandraa, Yamac Akgunb, Sara Zarnegarb, Kun Zhaob, Amibeth Gardnerb, Susan Hendersonb, Richard Ricardob, Yingda Wangb, Michael Christensenb
aVanderbilt University Medical Center, Nashville, TN, USA; bVUMC, Nashville, TN, USA
Chromoanagenesis is a catastrophic process that leads to acquisition of multiple genomic aberrations in one or several regions of chromosomes. Clinically significant gene fusion transcripts have been reported due to chromoanagenesis itself. We present two cases of early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) referred November 2021 and January 2022, with immunophenotype negative for CD1a, no T-cell receptor gamma chain (TRG) rearrangement. Each had complex clustered structural and numerical aberrations, rare but recurrent chromosomal translocations reported in ETP-ALL. Bone marrow (BM) biopsy could not be performed; therefore, peripheral blood (PB) was used for analysis.
Case 1: A 14-year-old male with no past medical history referred for anemia, thrombocytopenia, white blood cell (WBC) 147,000/uL, 97% blasts. Chest CT showed extensive mediastinal mass encasing the mediastinal vasculature and cerebrospinal fluid (CSF) was negative for leukemia, a t(10;11)(p12;q14.1) involving PICALM::AF10 rearrangement, complex aberrations and loss of TP53 in 70% of the cells. Clinical presentation of this translocation includes organomegaly, no central nervous system (CNS) involvement and hyperleukocytosis as seen in our case.
Case 2: A previously healthy 12-year-old female was referred for hyperleukocytosis, fever and abdominal pain with WBC count 653,000/uL, a translocation of t(8;12) with ETV6::NCOA2 rearrangement, complex aberrations in 100% of cells.
Case 1 has significant residual disease following induction and Case 2 is undergoing induction right now, remission status unknown.
Given that clustered aberrations were detected in PB instead of BM, we propose that chromoanasynthesis is the mechanism for localized shattering and reshuffling of the chromosomal regions in these cases.