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Case Reports
. 2024 Oct 15;12(10):2339.
doi: 10.3390/biomedicines12102339.

Blast Transformation of Chronic Myeloid Leukemia Driven by Acquisition of t(8;21)(q22;q22)/ RUNX1::RUNX1T1: Selecting Optimal Treatment Based on Clinical and Molecular Findings

Adolfo Fernández-Sánchez  1 , Alberto Hernández-Sánchez  1 , Cristina De Ramón  1 , María-Carmen Chillón  1 , María Belén Vidriales  1 , Mónica Baile-González  1 , Cristina-Teresa Fuentes-Morales  1 , Magdalena Sierra-Pacho  1 , Lucía López-Corral  1 , Fermín Sánchez-Guijo  1
Affiliations
Case Reports

Blast Transformation of Chronic Myeloid Leukemia Driven by Acquisition of t(8;21)(q22;q22)/ RUNX1::RUNX1T1: Selecting Optimal Treatment Based on Clinical and Molecular Findings

Adolfo Fernández-Sánchez et al. Biomedicines. .

Abstract

The advent of tyrosine kinase inhibitors (TKIs) has changed the natural history of chronic myeloid leukemia (CML), and the transformation from the chronic phase to the blast phase (BP) is currently an uncommon situation. However, it is one of the major remaining challenges in the management of this disease, as it is associated with dismal outcomes. We report the case of a 63-year-old woman with a history of CML with poor response to imatinib who progressed to myeloid BP-CML, driven by the acquisition of t(8;21)(q22;q22)/RUNX1::RUNX1T1. The patient received intensive chemotherapy and dasatinib, followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, she suffered an early relapse after allo-HSCT with the acquisition of the T315I mutation in ABL1. Ponatinib and azacitidine were started as salvage treatment, allowing for the achievement of complete remission with deep molecular response after five cycles. Advances in the knowledge of disease biology and clonal evolution are crucial for optimal treatment selection, which ultimately translates into better patient outcomes.

Keywords: T315I mutation; blast phase; chronic myeloid leukemia; core binding factor rearrangement.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Cytogenetic studies of the patient at myeloid BP-CML, showing the acquisition of t(8;21)(q22;q22)/RUNX1::RUNX1T1 as the driver event of BP. (a): BCR::ABL1 fusion probe (Dual Color, Dual Fusion, Vysis LSI) in the FISH study, showing two fusions in most of the cells, representative of the presence of t(9;22)(q34.1;q11.2)/BCR::ABL1 (b): RUNX1::RUNX1T1 fusion probe (Dual Color, Dual Fusion, Vysis LSI) in the FISH study, showing two fusions in approximately half of the cells, representative of the presence of t(8;21)(q22;q22)/RUNX1::RUNX1T1 (c): A Circos plot of optical genome mapping (Bionano) showing concomitant t(8;21)(q22;q22)/RUNX1::RUNX1T1 and t(9;22)(q34.1;q11.2)/BCR::ABL1 in the patient sample.
Figure 2
Figure 2
Polymerase chain reaction and Sanger sequencing analysis of T315I mutation in BCR::ABL1 fusion gene (c.944C > T, p.Thr315Ile).
Figure 3
Figure 3
A summary of the clinical case report. The temporal evolution of the BCR::ABL1/ABL1 ratio according to the International Scale (represented in blue) and the number of RUNX1::RUNX1T1 transcripts (represented in red) in peripheral blood samples are shown, together with the main events that the patient presented during the disease evolution. CML: chronic myeloid leukemia; BP: blast phase; FLAG-IDA: fludarabine, cytarabine, idarubicin and granulocyte colony-stimulating factor; allo-HCST: allogenic hematopoietic stem cell transplantation; MR: molecular response.
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