Lamin B1 deletion in myeloid neoplasms causes nuclear anomaly and altered hematopoietic stem cell function

Cell Stem Cell. 2022 Apr 7;29(4):577-592.e8. doi: 10.1016/j.stem.2022.02.010. Epub 2022 Mar 11.


Abnormal nuclear morphology is a hallmark of malignant cells widely used in cancer diagnosis. Pelger-Huët anomaly (PHA) is a common abnormality of neutrophil nuclear morphology of unknown molecular etiology in myeloid neoplasms (MNs). We show that loss of nuclear lamin B1 (LMNB1) encoded on chromosome 5q, which is frequently deleted in MNs, induces defects in nuclear morphology and human hematopoietic stem cell (HSC) function associated with malignancy. LMNB1 deficiency alters genome organization inducing in vitro and in vivo expansion of HSCs, myeloid-biased differentiation with impaired lymphoid commitment, and genome instability due to defective DNA damage repair. Nuclear dysmorphology of neutrophils in patients with MNs is associated with 5q deletions spanning the LMNB1 locus, and lamin B1 loss is both necessary and sufficient to cause PHA in normal and 5q-deleted neutrophils. LMNB1 loss thus causes acquired PHA and links abnormal nuclear morphology with HSCs and progenitor cell fate determination via genome organization.

Keywords: 3D genome; 5q deletions; genome instability; hematopoietic stem and progenitor cells; lineage determination; myeloid neoplasms; neutrophils; nuclear lamins; nuclear morphology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Nucleus
  • Hematopoietic Stem Cells / pathology
  • Humans
  • Lamin Type B / genetics
  • Myeloproliferative Disorders*
  • Neoplasms*
  • Pelger-Huet Anomaly* / genetics
  • Pelger-Huet Anomaly* / pathology


  • Lamin Type B
  • lamin B1