The role of next-generation sequencing in hematologic malignancies

Young‑Uk Cho

doi:10.1007/s44313-024-00010-0

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REVIEW

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Blood Res (2024) 59:11

Published online March 6, 2024

https://doi.org/10.1007/s44313-024-00010-0

The role of next-generation sequencing in hematologic malignancies

Young‑Uk Cho^1*

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¹Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic‑Ro 43‑Gil, Songpa‑Gu, Seoul 05505, Korea

Correspondence to : *Young‑Uk Cho
yucho@amc.seoul.kr

Received: January 17, 2024; Accepted: February 13, 2024

Abstract

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Abstract

Next-generation sequencing (NGS) allows high-throughput detection of molecular changes in tumors. Over the past 15 years, NGS has rapidly evolved from a promising research tool to a core component of the clinical laboratory. Sequencing of tumor cells provides an important step in detecting somatic driver mutations that not only characterize the disease but also influence treatment decisions. For patients with hematologic malignancies, NGS has been used for accurate classification and diagnosis based on genetic alterations. The recently revised World Health Organization classification and the European LeukemiaNet recommendations for acute myeloid leukemia consider genetic abnormalities as a top priority for diagnosis, prognostication, monitoring of measurable residual disease, and treatment choice. This review aims to present the role and utility of various NGS approaches for the diagnosis, treatment, and follow-up of hemato-oncology patients.

Keywords Next-generation sequencing, Leukemia, Diagnosis, Prognosis, Monitoring

Article

REVIEW

Blood Res 2024; 59():

Published online March 6, 2024 https://doi.org/10.1007/s44313-024-00010-0

The role of next-generation sequencing in hematologic malignancies

Young‑Uk Cho^1*

¹Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic‑Ro 43‑Gil, Songpa‑Gu, Seoul 05505, Korea

Correspondence to:*Young‑Uk Cho
yucho@amc.seoul.kr

Received: January 17, 2024; Accepted: February 13, 2024

Abstract

Keywords: Next-generation sequencing, Leukemia, Diagnosis, Prognosis, Monitoring

Abstract

Table 1 . Genetic variants detectable by next-generation sequencing assay and of clinical utility in hematologic malignancies.

Diseases	Mutated genes	Fusions
Myeloid malignancies	ABL1, ANKRD26, ASXL1^a,b, BCOR^a,b, BCORL1^a, BRCC3^a, CALR^c, CBL^a, CEBPA^c, CTCF^a, DDX41^c, DNMT3A^a, ETNK1, ETV6^c, EZH2^b,c, FLT3^c,d, GNAS^a, GNB1^a, IDH1^a,c, IDH2^a,c, JAK2^a,c, KIT^c, KMT2A^d, KRAS^a,c, MPL^c, NPM1^c, NRAS^a,c, PPM1D^a, PTPN11^a,c, RAD21^c, RUNX1^c, SETBP1^a, SF3B1^a,b,c, SH2B3, SRSF2^a,b,c, STAG2^b,c, TET2^a, TP53^a,c, U2AF1^a,b,c, WT1^c, ZBTB33^a, ZRSR2^b	BCR::ABL1, CBFB::MYH11, DEK::NUP214, KMT2Ar, MECOMr, NUP98r, PML::RARA, RBM15::MRTFA, RUNX1::RUNX1T1,
Lymphoid malignanciese	BRAF, CXCR4, CYLD, DIS3, EGR1, FAM46C, FGFR3, HIST1H1E, ID3, IRF4, KRAS, LTB, MAX, MYD88, NRAS, PAX5, RB1, STAT3, STAT5B, TCF3, TP53, TRAF3	ABL1r^f, ABL2r^f, BCR::ABL1, CRLF2r^f, CSF1Rr^f, DGKHr^f, DUX4r, EPORr^f, ETV6::RUNX1, IGH::IL3, other IGHr, IL2RBr^f, JAK2r^f, KMT2Ar, MEF2Dr, MYCr, NTRK3r^f, NUTM1r, PAX5r, PGDFRBr^f, PTK2Br^f, TCF3::PBX1, TCF3::HLF, TSLPr^f, TYK2r^f, ZNF384r

All genes are listed alphabetically.

^a Genes commonly mutated in clonal hematopoiesis [1].

^b Presence of mutations in these genes defines the category ‘acute myeloid leukemia myelodysplasia-related’ according to the WHO 2022 classification [1].

^c Basic set of genes provided by the ELN guideline may be useful in a panel approach for measurable residual disease monitoring in acute myeloid leukemia [18].

^d Reliable detection of FLT3-internal tandem duplication or KMT2A-partial tandem duplication using targeted NGS assay may require specialized bioinformatics analysis.

^e Only genetic aberrations in blood- or bone marrow-derived lymphoid malignancies were considered.

^f These genes are typically involved in gene fusions that characterize BCR::ABL1-like features.