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In recent classifications of hematological malignancies, disease subtypes are defined by key recurrent genetic alterations detected by conventional methods (i.e., cytogenetics, fluorescence in situ hybridization, and targeted sequencing). Hematological malignancies were also one of the first disease areas in which targeted therapies were introduced, the prime example being BCR::ABL1 inhibitors, followed by an increasing number of targeted inhibitors hitting the Achilles\u2019 heel of each disease, resulting in a clear patient benefit. Owing to the technical advances in high\u2010throughput sequencing, we can now apply broad genomic tests, including comprehensive gene panels or whole\u2010genome and whole\u2010transcriptome sequencing, to identify clinically important diagnostic, prognostic, and predictive markers. In this review, we give examples of how precision diagnostics has been implemented to guide treatment selection and improve survival in myeloid (myelodysplastic syndromes and acute myeloid leukemia) and lymphoid malignancies (acute lymphoblastic leukemia, diffuse large B\u2010cell lymphoma, and chronic lymphocytic leukemia). We discuss the relevance and potential of monitoring measurable residual disease using ultra\u2010sensitive techniques to assess therapy response and detect early relapses. Finally, we bring up the promising avenue of functional precision medicine, combining ex vivo drug screening with various omics technologies, to provide novel treatment options for patients with advanced disease. Although we are only in the beginning of the field of precision hematology, we foresee rapid development with new types of diagnostics and treatment strategies becoming available to the benefit of our patients.<\/jats:p>","DOI":"10.1111\/joim.13697","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T06:16:29Z","timestamp":1688969789000},"page":"413-436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Novel precision medicine approaches and treatment strategies in hematological malignancies"],"prefix":"10.1111","volume":"294","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0211-8788","authenticated-orcid":false,"given":"Richard","family":"Rosenquist","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden"},{"name":"Clinical Genetics Karolinska University Hospital, Solna Stockholm 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