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<p>Myelodysplastic neoplasms (MDS) disrupt bone marrow hematopoiesis, yet clinical assessment relies largely on blast enumeration and qualitative morphology, which incompletely capture marrow architecture and disease state. We applied whole-slide multiplex immunofluorescence imaging with single-cell phenotyping to map bone marrow microarchitecture in MDS. Diagnostic biopsies (<i>n</i> = 36), longitudinal treatment samples (<i>n</i> = 29), precursor states (<i>n</i> = 13), and normal controls (<i>n</i> = 21) were analyzed, comprising &gt;5 million spatially resolved cells. MDS marrow exhibited coordinated, genotype-imprinted architectural remodeling, including altered progenitor composition and spatial patterning, disrupted erythroid island organization, and displacement of hematopoietic stem and progenitor cells from perivascular niches. Interrogation of 82 cellular and spatial features yielded a composite Microarchitectural Perturbation Score (MDS-MAPS), derived from diagnostic samples and fixed prior to longitudinal analyses. In leave-one-patient-out cross-validation, MDS-MAPS discriminated remission from active disease more accurately than blast percentage (AUC 0.883 vs 0.660) and distinguished low-blast MDS from clonal cytopenia of undetermined significance (CCUS) (AUC 0.815). Mixed-effects modeling showed MAPS decreased in remission statistically independent of blast burden, with architectural normalization during remission and re-emergence at relapse. These findings define quantitative bone marrow architecture as a dynamic tissue-state biomarker that complements molecular and blast-based assessment in MDS.</p>

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Spatial remodeling of bone marrow architecture defines tissue-state signatures of disease activity and therapeutic response in myelodysplastic neoplasms

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月30日

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  • Ryan Nachman,
  • Aleksandra Kopacz,
  • Caitlin Unkenholz,
  • Jian Chai,
  • Arvin Ruiz,
  • Itzel Valencia,
  • Jeanne Jiang,
  • Fabio Socciarelli,
  • Jiwoon Park,
  • Christopher E. Mason,
  • Ling Zhang,
  • David Sallman,
  • Gail J. Roboz,
  • Pinkal Desai,
  • Justin Kaner,
  • Joshua Fein,
  • Monica Guzman,
  • Neal Lindeman,
  • Amy Chadburn,
  • Madhu Ouseph,
  • Paul Simonson,
  • Julia Geyer,
  • Giorgio Inghirami,
  • Shahin Rafii,
  • David Redmond,
  • Sanjay S. Patel

摘要

Myelodysplastic neoplasms (MDS) disrupt bone marrow hematopoiesis, yet clinical assessment relies largely on blast enumeration and qualitative morphology, which incompletely capture marrow architecture and disease state. We applied whole-slide multiplex immunofluorescence imaging with single-cell phenotyping to map bone marrow microarchitecture in MDS. Diagnostic biopsies (n = 36), longitudinal treatment samples (n = 29), precursor states (n = 13), and normal controls (n = 21) were analyzed, comprising >5 million spatially resolved cells. MDS marrow exhibited coordinated, genotype-imprinted architectural remodeling, including altered progenitor composition and spatial patterning, disrupted erythroid island organization, and displacement of hematopoietic stem and progenitor cells from perivascular niches. Interrogation of 82 cellular and spatial features yielded a composite Microarchitectural Perturbation Score (MDS-MAPS), derived from diagnostic samples and fixed prior to longitudinal analyses. In leave-one-patient-out cross-validation, MDS-MAPS discriminated remission from active disease more accurately than blast percentage (AUC 0.883 vs 0.660) and distinguished low-blast MDS from clonal cytopenia of undetermined significance (CCUS) (AUC 0.815). Mixed-effects modeling showed MAPS decreased in remission statistically independent of blast burden, with architectural normalization during remission and re-emergence at relapse. These findings define quantitative bone marrow architecture as a dynamic tissue-state biomarker that complements molecular and blast-based assessment in MDS.