DNA Damage Response (DDR) Is Associated With Treatment-free Remission in Chronic Myeloid Leukemia Patients

Malighetti, Federica; Arosio, G; Manfroni, Chiara; Mauri, Mario; Villa, Matteo; Manghisi, Beatrice; Inzoli, Elena; Rindone, Giovanni; Zambrotta, Giovanni Paolo Maria; Civettini, Ivan; Guglielmana, Veronica; Ramazzotti, Daniele; Giudici, Giovanni; Bombelli, S; Perego, R; Mologni, Luca; Gambacorti‐Passerini, Carlo

doi:10.1097/hs9.0000000000000852

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“…Indeed, nowadays, we know that, in another clinical setting, a second successful discontinuation attempt can take place after the failure of a first attempt [36]. A possible biological explanation resides in the progressive exhaustion of quiescent LSC [37,38]. Making a parallelism with the clinical history of our patient, we could speculate that, if his quiescent LSCs were the reason of his CML relapse almost 20 years after allogeneic HSCT, their eventual exhaustion after the time of a subsequent course of TKI therapy (never received before), leading to a sustained DMR (and even to stable undetectable transcript levels for 14 months before discontinuation) could support a subsequent stable TFR state.…”

Section: Tablementioning

confidence: 99%

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

Fontana,

Zambrotta,

Scannella

et al. 2024

Ann Hematol

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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.

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Section: Tablementioning

confidence: 99%