Exploring Experimental Hematology: May 2025 (Volumes 143 & 145)

Read highlights of the following articles from Experimental Hematology, volumes 143 and 145.

A distinct alternative mRNA splicing profile identifies the oncogenic CD44 transcript variant 3 in KMT2A-rearranged pediatric T-cell acute lymphoblastic leukemia cells.
Ramilo Amor, Amanda et al.
Experimental Hematology, Volume 145, 104712

The recent FDA approval of menin inhibitors targeting key genetic drivers of myeloid leukemia, such as KMT2A (lysine methyl transferase 2A) rearrangements and NPM1 mutations, has drawn attention to a recent article in press in Experimental Hematology. 

KMT2A rearrangement (KMT2A-r) is associated with a poorer prognosis in myeloid and lymphoid leukemia. The study is focused on the KMT2A rearrangement in T-ALL and how it is distinct from KMT2A-negative (KMT2A-wt) T-ALL.  

The authors performed transcriptome profiling on 171 primary T-ALL samples (n=161 wt vs n=10 KMT2A rearranged samples). They found that 15% of the genes were significantly differentially expressed in samples from patients with KMT2A-r T-ALL compared with samples from patients with KMT2A-wt T-ALL, with most of these (88%) being upregulated. 

miR1915 and ESPR1 were found highly upregulated in the KMT2A-r samples. However, high expression of miR1915 did not affect the expression of the BCL-2 family of proteins, which is often related to drug resistance in different tumor types. In contrast, the authors found that ESRP1 (Epithelial Splicing Regulatory Protein 1), a splicing protein, regulated the splice forms of the BCL-2 family of proteins. Overrepresentation analysis and ChIP-PCR further revealed CD44 variant 3 could be considered as a potential biomarker for KMT2Ar-T-ALL.
 

Further studies are warranted to assess how these KMT2Ar T-cells would respond to the family of BH3 mimetics and or the Menin inhibitors. 

Sex differences alter primitive progenitors in the C57BL/6 Tet2 knockout mouse model.
Holmes, Samantha M. et al.
Experimental Hematology, Volume 145, 104747
 

The study highlights the importance of considering sex differences in hematopoietic stem and progenitor cell populations and the need for maintaining equal numbers of males and females in mouse studies, especially in transgenic mouse models. 

Reconsidering the usual suspects in age-related hematologic disorders: Is stem cell dysfunction a root cause of aging?
Fotopoulou, Foteini et al.
Experimental Hematology, Volume 143, 104698

Fotopoulou, Foteini et al. discuss how aging impacts the entire hematopoietic system, particularly the weakening of the adaptive immune system. They also discuss how aged immune cells drive chronic inflammation ("inflammaging"), accelerating tissue damage and disease progression. The review illustrates the necessity of considering the roles of stem and mature blood cells in aging when developing effective rejuvenation interventions.

Blog post contributed by Nithya Balasundaram (X: @Nithya029) of the ISEH Publications Committee. 

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