Genetic lesions of IKZF1 are frequent events and well-established markers of adverse risk in acute lymphoblastic leukemia. However, their function in the pathophysiology and impact on patient outcome in acute myeloid leukemia (AML) remains elusive. In a multicenter cohort of 1606 newly diagnosed and intensively treated adult AML patients, we found IKZF1 alterations in 45 cases with a mutational hotspot at N159S. AML with mutated IKZF1 was associated with alterations in RUNX1, GATA2, KRAS, KIT, SF3B1, and ETV6, while alterations of NPM1, TET2, FLT3-ITD, and normal karyotypes were less frequent. The clinical phenotype of IKZF1-mutated AML was dominated by anemia and thrombocytopenia. In both univariable and multivariable analyses adjusting for age, de novo and secondary AML, and ELN2022 risk categories, we found mutated IKZF1 to be an independent marker of adverse risk regarding complete remission rate, event-free, relapse-free, and overall survival. The deleterious effects of mutated IKZF1 also prevailed in patients who underwent allogeneic hematopoietic stem cell transplantation (n = 519) in both univariable and multivariable models. These dismal outcomes are only partially explained by the hotspot mutation N159S. Our findings suggest a role for IKZF1 mutation status in AML risk modeling.

• MeSH
• akutní myeloidní leukemie * patologie   MeSH
• dospělí MeSH
• lidé MeSH
• mutace MeSH
• nukleofosmin MeSH
• prognóza MeSH
• transkripční faktor Ikaros genetika   MeSH
• transkripční faktory genetika   MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• tyrosinkinasa 3 podobná fms genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• IKZF1 protein, human MeSH Prohlížeč
• nukleofosmin MeSH
• transkripční faktor Ikaros MeSH
• transkripční faktory MeSH
• tyrosinkinasa 3 podobná fms MeSH

Near-haploid acute lymphoblastic leukemia is rare subgroup of the disease, which is very important due to very poor prognosis and resistance to treatment including novel monoclonal antibodies and CAR-T therapy.

• Klíčová slova
• CAR‐T therapy, acute lymphoblastic leukemia, blinatumomab, inotuzumab ozogamicin, near‐haploid,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH