Journal Article

DKFZ-2026-02190

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Functional characterization of snoRNA-derived RNA (sdRNA) expression in healthy hematopoiesis and acute myeloid leukemia.

Zinz, R. ; Rohde, C. ; Pauli, C. (First author)DKFZ* ; Zhou, F. ; Syed, A. A.DKFZ* ; Heid, D. ; Shah, V. ; Wahl, N. A. ; Ray, A.DKFZ* ; Renders, S. ; Werner, L. ; Förmer, S. ; Ahrens, C. ; Baldus, C. ; Bornhäuser, M. ; Röllig, C. ; Serve, H. ; Sauer, T. ; Krijgsveld, J.DKFZ* ; Müller-Tidow, C. ; Blank, M. (Last author)DKFZ*

2026
Springer Nature London

Abstract: SnoRNAs are highly expressed in AML and have implications in leukemogenesis and leukemic maintenance. SnoRNAs can be further processed into snoRNA-derived RNAs (sdRNAs). The role of sdRNAs in AML and healthy hematopoiesis remains largely elusive. We characterized sdRNA and snoRNA levels in hematopoietic stem and progenitor cells (HSPCs), healthy WBCs, and 159 intensively treated AML patient samples at initial diagnosis. HSPCs, healthy WBCs, and AML blasts could be differentiated by their sdRNA expression pattern in a cell-type-specific manner. In AML, high sd3'-RNA/snoRNA-host gene ratios were associated with an inverse patient outcome. Particularly, in NPM1-mutated patients with favorable risk stratification and good initial therapy response, high sd3'-RNA ratios identified a subgroup with inferior outcome. High sd3'-RNA ratios were associated with altered oncogenic, inflammatory, and immune response signaling. Forced expression of single sdRNAs, such as sd3'-SNORD78, sd3'-SNORD76, and sd5'-SNORD93, enhanced clonogenic potential in AML and drove sdRNA-specific gene expression signatures in both AML and healthy HSPCs. Exemplarily, we propose and characterize NUDT21, an important regulator of alternative polyadenylation and oncogenic gene expression, as a downstream target of sd3'-SNORD78 in AML. Our data introduce sdRNAs as standalone regulatory effector molecules in healthy hematopoiesis and AML.

Note: #EA:A350#LA:B230# / epub

---

Contributing Institute(s):

1. Reguläre Mechanismen der Genexpression (A350)
2. Proteomik von Stammzellen und Krebs (B230)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2026

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---