Late relapse of chronic myeloid leukemia after allogeneic bone marrow transplantation points to KANSARL (KANSL1::ARL17A) alteration: a case report with insights on the molecular landscape

Abstract

Chronic myeloid leukemia is a myeloproliferative neoplasm characterized by the presence of the Philadelphia chromosome and the consequent BCR::ABL1 oncoprotein. In the era before the introduction of tyrosine kinase inhibitors (TKIs), the only potentially curative treatment was allogeneic hematopoietic stem cell transplantation (HSCT). Here, we present the case of a patient affected by CML who experienced a relapse 20 years after allogeneic HSCT. Following relapse, the patient was treated with imatinib and bosutinib, resulting in a deep molecular response and successfully discontinued treatment. Additional analysis including whole-exome sequencing and RNA sequencing provided some insights on the molecular mechanisms of the relapse: the identification of the fusion transcript KANSL1::ARL17A (KANSARL), a cancer predisposition fusion gene, could justify a condition of genomic instability which may be associated with the onset and/or probably the late relapse of his CML.

Keywords: BCR::ABL1; CML; KANSARL; Late relapse; Next-generation sequencing.

Fig. 1

A Copy number plot (relapse vs. diagnosis). The black arrow points to an amplification of the whole chromosome 8; the red arrows point to deletions occurring in chromosomes 17 and 18. B Individual view of chromosome 8 (relapse vs diagnosis). Thick red horizontal bar identifies copy gain region. C Individual view of chromosome 17 (relapse vs. diagnosis). Thick green horizontal bar identifies copy loss region. D Individual view of chromosome 18 (relapse vs. diagnosis). Thick green horizontal bar identifies copy loss region

Fig. 2

Individual view of chromosome 6 (relapse vs. diagnosis). No copy number alterations in genes encoding HLA complex are found

Fig. 3

Fusion genes present at diagnosis. The red line indicates BCR::ABL1 fusion gene, while the lavender line indicates KANSL1::ARL17A fusion gene