Knockdown of the Shwachman-Diamond syndrome gene, SBDS, induces galectin-1 expression and impairs cell growth

Int J Hematol. 2024 Apr;119(4):383-391. doi: 10.1007/s12185-024-03709-z. Epub 2024 Jan 19.


Shwachman-Diamond syndrome (SDS) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency and bone marrow failure. The depletion of SBDS protein by RNA interference has been shown to cause inhibition of cell proliferation in several cell lines. However, the precise mechanism by which the loss of SBDS leads to inhibition of cell growth remains unknown. To evaluate the impaired growth of SBDS-knockdown cells, we analyzed Epstein-Barr virus-transformed lymphoblast cells (LCLs) derived from two patients with SDS (c. 183_184TA > CT and c. 258 + 2 T > C). After 3 days of culture, the growth of LCL-SDS cell lines was considerably less than that of control donor cells. By annealing control primer-based GeneFishing PCR screening, we found that galectin-1 (Gal-1) mRNA expression was elevated in LCL-SDS cells. Western blot analysis showed that the level of Gal-1 protein expression was also increased in LCL-SDS cells as well as in SBDS-knockdown 32Dcl3 murine myeloid cells. We confirmed that recombinant Gal-1 inhibited the proliferation of both LCL-control and LCL-SDS cells and induced apoptosis (as determined by annexin V-positive staining). These results suggest that the overexpression of Gal-1 contributes to abnormal cell growth in SBDS-deficient cells.

Keywords: Bone marrow failure; Maturation; Neutropenia; Neutrophil; SBDS.

MeSH terms

  • Animals
  • Benzamides*
  • Bone Marrow Diseases* / genetics
  • Cell Proliferation
  • Epstein-Barr Virus Infections*
  • Exocrine Pancreatic Insufficiency* / genetics
  • Exocrine Pancreatic Insufficiency* / metabolism
  • Galectin 1* / genetics
  • Herpesvirus 4, Human
  • Humans
  • Mice
  • Proteins
  • Shwachman-Diamond Syndrome
  • Tyrosine* / analogs & derivatives


  • 1-nitrohydroxyphenyl-N-benzoylalanine
  • Benzamides
  • Galectin 1
  • Proteins
  • SBDS protein, human
  • Tyrosine
  • LGALS1 protein, human