AML with Myelodysplasia-Related Changes: Development, Challenges, and Treatment Advances

Koenig, Kristin; Sahasrabudhe, Kieran; Sigmund, Audrey M.; Bhatnagar, Bhavana

doi:10.3390/genes11080845

Cited by 42 publications

(24 citation statements)

References 45 publications

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“…Therefore, it is of great significance to seek indicators for judging the prognosis and to guide the design of individualized treatment plans. The currently identified prognostic factors affecting AML mainly include the age, peripheral blood leukocyte count, secondary leukemia, and karyotype [ 22 ]. Among them, the karyotype is of great value to prognostic judgment, and there are obviously different treatment responses in patients with the same or normal karyotype immediately [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Regulatory Networks of Prognostic mRNAs in Pediatric Acute Myeloid Leukemia

Zhang

Cheng²,

Liu³

2022

Journal of Healthcare Engineering

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Acute myeloid leukemia (AML) in children refers to a malignant tumor caused by the abnormal proliferation of immature myeloid cells in the bone marrow and peripheral blood. The prognosis of patients with pediatric acute myeloid leukemia (AML) remains poor, highlighting the need for improved targeted therapy. The expression data of lncRNAs, mRNAs, and miRNAs and survival information of pediatric AML patients were collected from The Cancer Genome Atlas (TCGA) database. Cox regression analysis was used to screen the lncRNAs, mRNAs, and miRNAs that significantly affect the overall survival (OS) of patients as OS-related genes (included lncRNAs, mRNAs, and miRNAs). Enrichment analysis and protein-protein interaction (PPI) network construction were performed for the OS-related mRNAs. We further established a ceRNAs regulatory network. In addition, the potential prognostic role of genes was further evaluated by risk score. We have identified 5275 lncRNAs, 176 miRNAs, and 6221 mRNAs that significantly affect the prognosis of pediatric AML patients. It is worth noting that OS-related mRNAs are mainly involved in ribosome, RNA transport, and spliceosome. We identified the top 10 most connected mRNAs in the PPI network as important mRNAs and constructed a ceRNAs regulatory network (including NCBP2, RPLP0, UBC, RPS2, and RPS9). The risk score and nomogram results suggest that NCBP2 may be a risk factor for pediatric AML, while RPLP0, UBC, RPS2, and RPS9 may be protective factors. Our results construct 5 gene signals as new prognostic indicators for predicting the survival of pediatric AML patients. Our research has demonstrated the ceRNAs regulatory network may become a new target for pediatric AML treatment.

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Section: Discussionmentioning

confidence: 99%

Regulatory Networks of Prognostic mRNAs in Pediatric Acute Myeloid Leukemia

Zhang

Cheng²,

Liu³

2022

Journal of Healthcare Engineering

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“…Only adults with AML ≥ 60 years (n = 102) showed a slightly higher immune cell abundance in comparison to children with AML [29]. This may be related to the increased prevalence of myelodysplastic syndrome-related AML in older adults as this subtype is associated with relatively high levels of immune infiltration in the bone marrow [45,46].…”

Section: Immune Cells In the Tme Of Aml At Diagnosismentioning

confidence: 99%

Paving the Way for Immunotherapy in Pediatric Acute Myeloid Leukemia: Current Knowledge and the Way Forward

Koedijk

Werf

Calkoen

et al. 2021

Cancers

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Immunotherapeutic agents may be an attractive option to further improve outcomes and to reduce treatment-related toxicity for pediatric AML. While improvements in outcome have been observed with immunotherapy in many cancer types, immunotherapy development and implementation into patient care for both adult and pediatric AML has been hampered by an incomplete understanding of the bone marrow environment and a paucity of tumor-specific antigens. Since only a minority of patients respond in most immunotherapy trials across different cancer types, it will be crucial to understand which children with AML are likely to respond to or may benefit from immunotherapies. Immune cell profiling efforts hold promise to answer this question, as illustrated by the development of predictive scores in solid cancers. Such information on the number and phenotype of immune cells during current treatment regimens will be pivotal to generate hypotheses on how and when to intervene with immunotherapy in pediatric AML. In this review, we discuss the current understanding of the number and phenotype of immune cells in the bone marrow in pediatric AML, ongoing immunotherapy trials and how comprehensive immune profiling efforts may pave the way for successful clinical trials (and, ultimately, implementation into patient care).

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“…Acute myeloid leukaemia (AML) is the most common myeloid leukaemia in adults characterized by an accumulation of immature myeloid cells [ 1 , 2 ]. Myelodysplastic Syndrome (MDS), another disease of myeloid origin is characterized by the perturbed function of the myeloid-erythroid-megakaryocytic lineage resulting in neutropenia, thrombocytopenia and anaemia [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Approximately 30% of the MDS patients develop overt AML during the course of the disease [ 4 ]. Compared with other haematological malignancies, the prognosis of MDS/AML is relatively poor, since it is mainly a disease of elderly patients who cannot tolerate intensive chemotherapy regimens [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumin as an Epigenetic Therapeutic Agent in Myelodysplastic Syndromes (MDS)

Xie

Frank

Patnana

et al. 2021

IJMS

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Growth Factor Independence 1 (GFI1) is a transcription factor with an important role in the regulation of development of myeloid and lymphoid cell lineages and was implicated in the development of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). Reduced expression of GFI1 or presence of the GFI1-36N (serine replaced with asparagine) variant leads to epigenetic changes in human and murine AML blasts and accelerated the development of leukaemia in a murine model of human MDS and AML. We and other groups previously showed that the GFI1-36N allele or reduced expression of GFI1 in human AML blasts is associated with an inferior prognosis. Using GFI1-36S, -36N -KD, NUP98-HOXD13-tg mice and curcumin (a natural histone acetyltransferase inhibitor (HATi)), we now demonstrate that expansion of GFI1-36N or –KD, NUP98-HODXD13 leukaemic cells can be delayed. Curcumin treatment significantly reduced AML progression in GFI1-36N or -KD mice and prolonged AML-free survival. Of note, curcumin treatment had no effect in GFI1-36S, NUP98-HODXD13 expressing mice. On a molecular level, curcumin treatment negatively affected open chromatin structure in the GFI1-36N or -KD haematopoietic cells but not GFI1-36S cells. Taken together, our study thus identified a therapeutic role for curcumin treatment in the treatment of AML patients (homo or heterozygous for GFI1-36N or reduced GFI1 expression) and possibly improved therapy outcome.

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AML with Myelodysplasia-Related Changes: Development, Challenges, and Treatment Advances

Cited by 42 publications

References 45 publications

Regulatory Networks of Prognostic mRNAs in Pediatric Acute Myeloid Leukemia

Regulatory Networks of Prognostic mRNAs in Pediatric Acute Myeloid Leukemia

Paving the Way for Immunotherapy in Pediatric Acute Myeloid Leukemia: Current Knowledge and the Way Forward

Curcumin as an Epigenetic Therapeutic Agent in Myelodysplastic Syndromes (MDS)

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