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. 2024 Jan 26;8(1):e26.
doi: 10.1002/hem3.26. eCollection 2024 Jan.

Hyperdiploid acute lymphoblastic leukemia in children with LZTR1 germline variants

Lisa Zipper  1 , Rabea Wagener  2 , Ute Fischer  2   3 , Anna Hoffmann  2 , Layal Yasin  2 , Danielle Brandes  2 , Stavrieta Soura  2 , Ammarah Anwar  2 , Carolin Walter  4 , Julian Varghese  4 , Julia Hauer  5 , Franziska Auer  5 , Sanil Bhatia  2 , Martin Dugas  6 , Stefanie V Junk  2   7 , Martin Stanulla  7 , Oskar A Haas  8 , Arndt Borkhardt  2   3 , Tobias Reiff  1 , Triantafyllia Brozou  2
Affiliations

Hyperdiploid acute lymphoblastic leukemia in children with LZTR1 germline variants

Lisa Zipper et al. Hemasphere. .
No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Depiction of the ten LZTR1 variants detected in the pediatric cohort of the 283 BCP‐ALL patients. Germline variants that were tested by applying the Drosophila model are highlighted in colored fonts. (B–G) Confocal images showing (B) Controls, (C–G) specific inducible knockdown (KD) of Drosophila Lztr1 (dLztr1), and simultaneous expression of (D) wild‐type human LZTR1 (hLZTR1 wt ), (E) variant hLZTR1 p.Arg283Trp , (F) hLZTR1 p.Tyr535Ter and (G) hLZTR1 p.Lys761Arg of adult Drosophila midguts after seven days of stem cell progeny tracing using esg ReDDM . (H) Quantification of intestinal stem cell (ISC) lineage production encompassing ISC, EB, and newly differentiated EC (GFP+ RFP+ and RFP+ cells) revealed an increase upon KD of dLztr1 and expression of variant hLZTR1 p.Tyr353Ter . (I) Progenitor cell death assessed by the number of dying ISC/EB is increased upon expression of variant hLZTR1 p.Tyr353Ter , (J) ERK phosphorylation as an indication of Ras activation induced by hLZTR1 p.Tyr353Ter . (K) Of note, recombination frequency revealed by loss of double fluorescence is increased by hLZTR1 p.Arg283Trp and hLZTR1 p.Tyr353Ter . Mean is indicated by (+) (n = 15,16,10,10,10,10 [H]; 11,12,7,10,10,10 [I]; 6,8,8,8,8,6 [J]; 19,20,10,10,10,10 [K]) and asterisks indicate significances from Student's t‐test (*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001). EB, enteroblasts; EC, enterocytes.
See this image and copyright information in PMC

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