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. 2025 Oct 1;110(10):2535-2542.
doi: 10.3324/haematol.2024.286815. Epub 2025 Feb 27.

Ex vivo drug response profiling guides therapy in a case of high-risk acute undifferentiated leukemia with PICALM::MLLT10

Elena Mastrodicasa  1 , Luca Pagliaro  2 , Valentina Pierini  3 , Valentina Bardelli  3 , Mariateresa Giaimo  2 , Raffaella Zamponi  4 , Anna Montanaro  4 , Katia Tragni  5 , Roberta Arcaleni  3 , Maria Speranza Massei  1 , Ilaria Capolsini  1 , Katia Perruccio  1 , Elena Varotto  6 , Barbara Buldini  6 , Andrea Gherli  4 , Silvia Romoli  3 , Caterina Matteucci  3 , Maria Crocioni  3 , Francesco Arcioni  1 , Grazia Gurdo  1 , Carla Cerri  1 , Maurizio Caniglia  1 , Giovanni Roti  2 , Roberta La Starza  7
Affiliations

Ex vivo drug response profiling guides therapy in a case of high-risk acute undifferentiated leukemia with PICALM::MLLT10

Elena Mastrodicasa et al. Haematologica. .
No abstract available

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Figures

Figure 1.
Figure 1.
Chemogenomic profiling identifies effective compounds for a translational purpose. (A) Light microscopy image of a bone marrow (BM) blood smear at diagnosis showing medium-sized undifferentiated blasts with prominent nucleoli and agranular basophilic cytoplasm. Scale bars, 10 μm. (B) Immunophenotype assessment at diagnosis showing a prevalent population of undifferentiated blasts. (See text for details.) (C) Cytogenetic assessment of the major clone. (Left) Karyotype of the major clone: 46,XY,t(10;11)(p12;q23). (Right) Fluorescence in situ hybridization analysis of the major clone: PICALM (RP11-12D16/RP11-90K17, green) plus MLLT10 (RP11-249M6/RP11-418C1, orange). (D) Lollipop graphs showing sequenced mutations in the exonic region of CIITA, EZH2, NF1, and SETD2 genes. Allelic variants are depicted with a circle (red, frameshift; blue, missense; orange, nonsense) relative to their amino acid position and their protein domains (color-coded). (E) Outline of the drug response profiling (DRP) platform. (F) Radar plot with a color indication from the drug class group showing the drug sensitivity scores (DSS) of each compound tested. DSS values (white and red dots) range from zero (center) to the maximum value (outside border). Red dots identify compounds with DSS ≥1 and AUC <300. (G) DSS values of compound classes by target identification with at least two representative compounds for each class. Bar colors identify the main compound class as in (F). AWS: associated with SET; CSR: cysteine- and serine-rich; GR: GAP-related; hr: hours; ImiD: immunomodulatory drugs; LRR: Leucine-rich repeats; SRI: Set2-Rpb1 interacting; RI: ribonuclease inhibitor-like.
Figure 2.
Figure 2.
The functional precision medicine approach induced measurable residual disease negativity and cytogenetic remission in a patient with refractory acute undifferentiated leukemia. (A) Timeline depicting the course of disease and treatment choice coupled with measurable residual disease (MRD) assessment. Colored lines correspond to the percentage of blasts at morphology (pink), flow cytometry (green), and percentage of nuclei at fluorescence in situ hybridization (FISH) analysis for del(5q) (blue), and t(10;11) PICALM::M-LLT10 (cyan). (B) (Top) Color boxes show the therapy schedules of the relative DRP-driven treatments depicted in (A); VEN-AML, venetoclax was administered orally (360 mg/m daily) from days 1 to 28, idarubicin (12 mg/m) on day 13, cytarabine (1,000 mg/m) twice daily from days 13 to 16. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) conditioning regimen consisted of total body irradiation (TBI), thiotepa (5 mg/kg) for 2 days, cyclophosphamide (15 mg/kg) for 2 days, and fludarabine (40 mg/m2) 4 days; T-regulatory cell (T-reg) infusion was performed as prophylaxis against graft-versus-host disease. (Bottom) Effect of the selected compounds on cell viability after 72 hours (hr) of treatments in the acute undifferentiated leukemia (AUL) patient’s sample (dark blue line) and a panel of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) cell lines (light blue lines). Cell lines: ALL/SIL, DND41, HSB-2, HNT-34, Jurkat, Loucy, MOLM-1, PF-382, SUPT-1, UCSD-AML1.
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References

    1. Liebers N, Bruch PM, Terzer T, et al. Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial. Nat Cancer. 2023;4(12):1648-1659. - PMC - PubMed
    1. Wang H, Chan KYY, Cheng CK, et al. Pharmacogenomic profiling of pediatric acute myeloid leukemia to identify therapeutic vulnerabilities and inform functional precision medicine. Blood Cancer Discov. 2022;3(6):516-535. - PMC - PubMed
    1. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36(7):1703-1719. - PMC - PubMed
    1. Alexander TB, Gu Z, Iacubicci I, et al. The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature. 2018;562(7727):373-379. - PMC - PubMed
    1. Hrusak O, de Haas V, Stancikova J, et al. International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia. Blood. 2018;132(3):264-276. - PubMed

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