Verification of prognostic expression biomarkers is improved by examining enriched leukemic blasts rather than mononuclear cells from acute myeloid leukemia patients

Pogosova-Agadjanyan, Era L.; Hua, Xing; Othus, Megan; Appelbaum, Frederick R.; Chauncey, Thomas R.; Erba, Harry P.; Fitzgibbon, Matthew P.; Jenkins, Isaac C.; Fang, Min; Lee, Stanley C.; Moseley, Anna; Naru, Jasmine; Radich, Jerald P.; Smith, Jenny L.; Willborg, Brooke E.; Willman, Cheryl L.; Wu, Feinan; Meshinchi, Soheil; Stirewalt, Derek L.

doi:10.1186/s40364-023-00461-0

Table 1 Comparison of significant pathways enriched by DEGs associated with cytogenetic risk in paired bulk MNCs versus VLBs

From: Verification of prognostic expression biomarkers is improved by examining enriched leukemic blasts rather than mononuclear cells from acute myeloid leukemia patients

Cytogenetic-Related Genes in MNCs (N = 392)			Cytogenetic-Related Genes in VLBs (N = 455)
Pathway Rank (N = 835)	Pathway Name	Entities FDR	Pathway Rank (N = 1020)	Pathway Name	Entities FDR
1	Phosphorylation of CD3 and TCR zeta chains	1.09E-11	1	Transcriptional regulation of granulopoiesis	8.70E-05
2	Translocation of ZAP-70 to Immunological synapse	2.46E-11	2	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport & efflux	0.003861
3	PD-1 signaling	4.86E-11	3	NR1H2 and NR1H3-mediated signaling	0.006610
4	Generation of second messenger molecules	2.46E-09	4	RUNX3 regulates CDKN1A transcription	0.061994
5	Neutrophil degranulation	4.79E-07	13	Neutrophil degranulation	0.450842
6	MHC class II antigen presentation	4.79E-07	53	Cytokine Signaling in Immune system	0.593232
7	Costimulation by the CD28 family	4.94E-07	90	Immune System	0.593232
8	Downstream TCR signaling	6.04E-05	128	Interferon Signaling	0.593232
9	TCR signaling	1.22E-04	359	MHC class II antigen presentation	0.593232
10	Interferon Signaling	7.42E-04	535	Generation of second messenger molecules	0.626337
11	Immune System	7.42E-04	687	Translocation of ZAP-70 to Immunological synapse	0.779539
12	Interferon gamma signaling	0.001212	718	Phosphorylation of CD3 and TCR zeta chains	0.802141
13	Cytokine Signaling in Immune system	0.003510	799	Costimulation by the CD28 family	0.871081
17	RUNX3 regulates CDKN1A transcription	0.107059	828	TCR signaling	0.898506
41	Transcriptional regulation of granulopoiesis	0.500239	991	Interferon gamma signaling	0.998825
55	NR1H2 and NR1H3-mediated signaling	0.557604	Not Identified	PD-1 signaling	N/A
59	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport & efflux	0.557604	Not Identified	Downstream TCR signaling	N/A

The lists of DEGs significantly associated with cytogenetic risk groups from paired bulk MNCs and VLBs were downloaded into Reactome to identify pathways enriched in the lists. Pathways significantly associated with cytogenetic risk in bulked MNCs and VLBs were examined separately. Table shows the significance and rank by FDR of individual pathways that were significant in MNCs and VLBs using the list derived from bulk MNCs (left columns) and VLBs (right columns). Those pathways significant associated with the list of genes from bulk MNCs and VLBs are highlighted in light blue and gold, respectively. The significant pathways identified in the bulk MNCs (N = 13) were not significantly enriched for in the VLBs, and vice versa

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ISSN: 2050-7771

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