Prognostic heterogeneity and clonal dynamics within distinct subgroups of myelodysplastic syndrome and acute myeloid leukemia with <i>TP53</i> disruptions

Patel, Shyam A.; Cerny, Jan; Gerber, William K.; Ramanathan, Muthalagu; Ediriwickrema, Asiri; Tanenbaum, Benjamin; Hutchinson, Lloyd; Meng, Xiuling; Flahive, Julie; Barton, Bruce; Gillis‐Smith, Andrew J.; Suzuki, Sakiko; Khedr, Salwa; Selove, William; Higgins, Anne W.; Miron, Patricia M.; Simin, Karl; Woda, Bruce; Gerber, Jonathan M.

doi:10.1002/jha2.791

Cited by 7 publications

(2 citation statements)

References 34 publications

(61 reference statements)

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“…There were no cases of CHIP/CCUS with TP53 or IDH1 mutations, partly because of the new nomenclature in the ICC which respects TP53 mutation within top‐line haematopathological diagnoses (these exclude CHIP/CCUS). Our separate query in 2023 of the UMass Leukemia Registry for TP53 aberrations yielded 76 patients, and 100% of these 76 patients carried a bona fide morphological diagnosis of MN 18 . Among the 94 patients with CHIP or CCUS, a variety of genomic aberrations were seen, with in‐frame substitutions (missense mutations) accounting for the majority (53.0%) of somatic variants (Figure 1D).…”

Section: Resultsmentioning

confidence: 99%

“…DNA was quantified by spectrophotometry/fluorometry. A library was created using multiplex PCR targeting oncogene ‘hot spot’ mutations and full exon sequencing of some tumour suppressor genes (CTMPv1 panel), as previously described by our group 12,17,18 . PCR amplicons were isolated, followed by the ligation of a sequencing linker and barcode for patient identification.…”

Section: Methodsmentioning

confidence: 99%

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Natural history of clonal haematopoiesis seen in real‐world haematology settings

Patel,

Gerber,

Zheng

et al. 2024

Br J Haematol

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SummaryRecursive partitioning of healthy consortia led to the development of the Clonal Hematopoiesis Risk Score (CHRS) for clonal haematopoiesis (CH); however, in the practical setting, most cases of CH are diagnosed after patients present with cytopenias or related symptoms. To address this real‐world population, we characterize the clinical trajectories of 94 patients with CH and distinguish CH harbouring canonical DNMT3A/TET2/ASXL1 mutations alone (‘sole DTA’) versus all other groups (‘non‐sole DTA’). TET2, rather than DNMT3A, was the most prevalent mutation in the real‐world setting. Sole DTA patients did not progress to myeloid neoplasm (MN) in the absence of acquisition of other mutations. Contrastingly, 14 (20.1%) of 67 non‐sole DTA patients progressed to MN. CHRS assessment showed a higher frequency of high‐risk CH in non‐sole DTA (vs. sole DTA) patients and in progressors (vs. non‐progressors). RUNX1 mutation conferred the strongest risk for progression to MN (odds ratio [OR] 10.27, 95% CI 2.00–52.69, p = 0.0053). The mean variant allele frequency across all genes was higher in progressors than in non‐progressors (36.9% ± 4.62% vs. 24.1% ± 1.67%, p = 0.0064). This analysis in the post‐CHRS era underscores the natural history of CH, providing insight into patterns of progression to MN.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%