{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:47:12Z","timestamp":1770814032677,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005363","name":"Universidad de Buenos Aires","doi-asserted-by":"publisher","award":["20720220100012BA"],"award-info":[{"award-number":["20720220100012BA"]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Pt A"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Chronic lymphocytic leukemia (CLL) is a highly heterogeneous B\u2010cell malignancy, spanning a spectrum from indolent conventional forms (C\u2010CLL) to Richter transformation. Accelerated CLL (A\u2010CLL) represents an intermediate subtype, histologically and clinically more aggressive than C\u2010CLL, yet its diagnosis relies on subjective histological criteria. We hypothesized that high\u2010dimensional single\u2010cell morphometrics from routine hematoxylin and eosin\u2010stained lymph node biopsies could provide complementary metrics for positioning cases along the disease continuum. We implemented a novel, open\u2010source methodology using CellProfiler and Seurat to segment cells and measure hundreds of parameters from two indolent and two aggressive cases. Datasets were integrated to mitigate technical batch effects. Our analysis combined an unsupervised approach with trajectory analysis and a pathologist\u2010guided supervised machine learning model. Both unsupervised and supervised approaches successfully and independently distinguished aggressive from indolent cases. Aggressive cases were enriched in morphometric clusters corresponding to paraimmunoblasts, while indolent cases were enriched in those corresponding to small lymphocytes. Pseudo\u2010bulk analysis using a subset of key parameters also successfully classified patients. In this highly exploratory, proof\u2010of\u2010concept study utilizing a small, well\u2010characterized cohort (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094 CLL patients plus 2 RT reference cases), we present a robust and traceable single\u2010cell morphometric pipeline. By providing objective metrics of cellular and subcellular morphology, our method reveals strong segregation patterns reflecting the CLL continuum. Our findings warrant validation in larger cohorts, but offer novel, quantifiable insights that could potentially complement diagnostic criteria and aid in patient stratification.\n                  <\/jats:p>","DOI":"10.1002\/cytoa.70010","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T07:29:31Z","timestamp":1768980571000},"page":"62-79","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell Morphometrics From Hematoxylin and Eosin\u2010Stained Images Reveals Subtype\u2010Specific Features in Chronic Lymphocytic Leukemia"],"prefix":"10.1002","volume":"109","author":[{"given":"Mar\u00eda Cecilia Cabral","family":"Lorenzo","sequence":"first","affiliation":[{"name":"Divisi\u00f3n Anatom\u00eda Patol\u00f3gica Hospital de Cl\u00ednicas \u201cJos\u00e9 de San Mart\u00edn\u201d, Facultad de Medicina, Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Quarroz Braghini","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n Anatom\u00eda Patol\u00f3gica Hospital de Cl\u00ednicas \u201cJos\u00e9 de San Mart\u00edn\u201d, Facultad de Medicina, Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregorio","family":"Cordini","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n Hematolog\u00eda Hospital de Cl\u00ednicas \u201cJos\u00e9 de San Mart\u00edn\u201d, Facultad de Medicina, Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom\u00e1s","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunotoxicolog\u00eda (LaITo) IDEHU\u2010CONICET, Hospital de Cl\u00ednicas \u201cJos\u00e9 de San Mart\u00edn\u201d Facultad de Medicina Universidad de Buenos Aires (UBA)  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Kornblihtt","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n Hematolog\u00eda Hospital de Cl\u00ednicas \u201cJos\u00e9 de San Mart\u00edn\u201d, Facultad de Medicina, Universidad de Buenos Aires  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2375-0077","authenticated-orcid":false,"given":"Guillermo","family":"Blanco","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunotoxicolog\u00eda (LaITo) IDEHU\u2010CONICET, Hospital de Cl\u00ednicas \u201cJos\u00e9 de San Mart\u00edn\u201d Facultad de Medicina Universidad de Buenos Aires (UBA)  Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2025.2513005"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27546"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199801000-00006"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2018.07.009"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.247"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198812000-00002"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.07.009"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2023.12.004"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0000000000001173"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02113-6"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2025.05.011"},{"key":"e_1_2_11_13_1","first-page":"14","article-title":"Richter 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