ID
55
Cancer Name
Acute Myeloid Leukemia (Adult)
Main Grouping
Hematologic
Organ System
Bone marrow, blood
Cell Origin
Myeloid precursor cells
Pathways Affected
Acute myeloid leukemia involves a pathway landscape defined by two classes of cooperating mutations: Class I signaling mutations that provide a proliferative/survival advantage (FLT3-ITD/TKD, NRAS, KRAS, KIT) and Class II epigenetic/transcription factor mutations that create differentiation block (DNMT3A, TET2, IDH1/2, EZH2, ASXL1, CEBPA, RUNX1, NPM1) — with both classes required for full leukemic transformation.
The FLT3/RAS/MAPK/ERK and PI3K/AKT/mTOR proliferative signaling pathway is constitutively activated in AML through FLT3-ITD (approximately 25 to 28 percent of AML), FLT3-TKD (approximately 7 to 8 percent), NRAS/KRAS activating mutations (approximately 15 percent combined), and KIT mutations (approximately 4 to 5 percent): FLT3-ITD creates constitutively dimerized and kinase-active FLT3 receptor through tandem duplication of the juxtamembrane domain, driving constitutive STAT5, RAS/MAPK/ERK, and PI3K/AKT/mTOR downstream signaling; FLT3-ITD uniquely activates STAT5 more potently than FLT3 wild-type, and STAT5-driven PIM kinases (PIM1/2) provide additional anti-apoptotic signaling in FLT3-ITD AML; FLT3-ITD also suppresses PU.1 and C/EBPalpha transcription factor activity creating differentiation block; quercetin inhibited p-AMPK and p-mTOR in HL-60 AML cells through the CaMKKbeta/AMPK/mTOR pathway confirmed by Western blot (PMC9827794); quercetin downregulated VEGF/PI3K/Akt signaling inducing mitochondria-mediated apoptosis in AML cells confirmed by MMP dissipation rescue experiment with PI3K/Akt activator (PMC7758733). The NF-kB inflammatory pathway is constitutively activated in AML through FLT3-ITD, RAS, and cytokine receptor signaling; NF-kB drives AML blast survival through BCL2, BCL-XL, and MCL-1 anti-apoptotic gene transcription; NF-kB also drives IL-1beta, IL-6, and TNF-alpha autocrine AML survival signaling; curcumin inhibits NF-kB and induces apoptosis in AML cell models; quercetin inhibits NF-kB in AML cell models.
The epigenetic dysregulation pathway is uniquely central to AML biology and is the most commonly mutated category of AML driver genes (~60-70% of AML cases carry at least one epigenetic regulator mutation): DNMT3A R882H mutations (~18-22% of AML) create a dominant-negative inhibitor of wild-type DNMT3A reducing methylation at CpG-rich enhancers of hematopoietic stem cell self-renewal genes (HOXA9, HOXA10, MEIS1, GATA2) preventing their silencing during differentiation; TET2 loss-of-function mutations (~7-23%) prevent conversion of 5-methylcytosine to 5-hydroxymethylcytosine impairing active DNA demethylation at enhancers of myeloid differentiation genes; IDH1 R132 and IDH2 R140/R172 gain-of-function mutations (~18-27% combined) generate the oncometabolite 2-hydroxyglutarate (2-HG) that competitively inhibits TET2, KDM histone demethylases, and EglN prolyl hydroxylases creating CIMP (CpG island methylator phenotype), histone hypermethylation (H3K4me3, H3K9me3, H3K27me3), and differentiation arrest; EZH2 mutations or PRC2 complex dysregulation (~2-5%) create H3K27me3 dysregulation at myeloid differentiation gene promoters; ASXL1 mutations (~5-11%) disrupt the PR-DUB complex that removes H2AK119ub1 impairing Polycomb-mediated gene regulation; quercetin eliminated DNMT1 and DNMT3a expression in HL-60 and U937 AML cells and downregulated class I HDACs and induced demethylation of BCL2L11, DAPK1, BAX, APAF1, BNIP3, and BNIP3L pro-apoptotic gene promoters with accumulation of acetylated H3 and H4 confirmed (PMC6225654) — directly targeting the dominant epigenetic driver landscape of AML.
The NPM1/ARF/p53 pathway is uniquely relevant in NPM1-mutant AML (~28-32%): NPM1 wild-type shuttles between nucleus and cytoplasm serving as an ARF-stabilizing platform that prevents MDM2-mediated p53 ubiquitination; NPM1 type A mutations create cytoplasmic localization sequence (NES-like motif) through 4bp insertion at exon 12 driving NPM1 cytoplasmic mislocalization; cytoplasmic NPM1mut disrupts nucleolar ARF function and impairs the ARF-MDM2-p53 pathway for oncogenic stress-induced apoptosis; NPM1mut also mis-regulates HOX gene transcription and retinoic acid receptor signaling; curcumin targets NPM1 cytoplasmic mislocalization in AML cell models; EGCG activates p53 pro-apoptotic signaling in AML.
The HOXA/HOXB gene transcription pathway is activated in the majority of AML regardless of cytogenetics: HOX gene overexpression (HOXA9, HOXA10, HOXB3, HOXB4) is documented in approximately 70 percent of AML cases and defines an AML stem cell-like transcriptional state; NPM1 mutations, MLL (KMT2A) rearrangements, and NUP98 fusions all drive HOXA/HOXB gene upregulation through different mechanisms; DNMT3A mutations impair silencing of HOXA cluster genes; plant polyphenols including EGCG, quercetin, and curcumin target the mTOR pathway that regulates HOXA gene transcription.
The autophagy pathway is uniquely relevant in AML: AML blasts suppress autophagy through FLT3-ITD/mTORC1 signaling creating autophagy deficiency that promotes AML blast survival and resistance to apoptosis; quercetin induced autophagy-associated cell death in HL-60 AML cells through CaMKKbeta/AMPK/mTOR pathway activation confirmed by LC3 II/I ratio increase, Beclin-1 upregulation, and p62 downregulation — directly reversing the FLT3-ITD/mTORC1-driven autophagy suppression in AML (PMC9827794). The apoptosis pathway is suppressed in AML through BCL2 overexpression (documented in ~75% of AML), MCL-1 upregulation, and FLT3-ITD/STAT5-driven PIM kinase anti-apoptotic signaling; quercetin downregulated MCL-1 in U937 AML cells; quercetin induced PARP cleavage in THP-1, MV4-11, and U937 AML cell lines (PMC8510366); quercetin demethylated pro-apoptotic BCL2L11 (BIM), DAPK1, BAX, APAF1, BNIP3, and BNIP3L genes in HL-60 and U937 AML cells (PMC6225654) targeting the BCL2/MCL-1-driven apoptosis suppression.
Description
Acute myeloid leukemia (AML) is the most common acute leukemia in adults, accounting for approximately 80 percent of adult acute leukemias. In the United States, an estimated 20,800 new AML cases and 11,220 deaths were projected for 2024, with AML being responsible for approximately 1.1 percent of all new cancer diagnoses. Globally, AML accounts for approximately 119,000 new cases and 98,000 deaths annually according to GLOBOCAN 2022. AML predominantly affects older adults with a median age at diagnosis of approximately 68 years, and the incidence increases sharply with age; AML in patients over 70 years has a 5-year overall survival of only approximately 5 to 10 percent compared with approximately 40 to 60 percent in younger patients.
The overall 5-year relative survival for AML across all ages is approximately 29 to 32 percent. By ELN 2022 risk group and age: favorable-risk younger adult AML (less than 60 years) achieves complete remission in approximately 80 to 90 percent and long-term overall survival of approximately 50 to 70 percent; intermediate-risk AML achieves approximately 40 to 60 percent long-term survival; adverse-risk AML achieves 5-year survival of approximately 10 to 25 percent; older patient AML (greater than 70 years) has approximately 5 to 15 percent 5-year survival.
The molecular landscape of adult AML is defined by cooperative mutations across multiple cellular processes: signaling pathway mutations (FLT3-ITD/TKD ~30-35%, NRAS ~10%, KRAS ~5%, KIT ~4-5%) that provide proliferative advantage; transcription factor mutations (CEBPA ~6-10%, RUNX1 ~10%, WT1 ~8-12%) that create differentiation block; epigenetic regulators (DNMT3A ~18-22%, TET2 ~7-23%, IDH1 ~7-12%, IDH2 ~10-15%, EZH2 ~2-5%, ASXL1 ~5-11%) that drive epigenetic deregulation; nucleophosmin (NPM1) mutations (~28-32%, the most common mutation); splicing factor mutations (SRSF2, SF3B1, U2AF1, ZRSR2 collectively ~15-20% in AML-MR); cohesin complex mutations (STAG2, RAD21, SMC1A, SMC3 ~5-10%); and TP53 mutations (~8-14%, associated with complex karyotype and extremely adverse prognosis).
Published laboratory research documents quercetin from plant foods inducing autophagy and apoptosis in HL-60 human AML cells through the CaMKKbeta/AMPK/mTOR signal pathway with confirmed AMPK/mTOR modulation and LC3-II autophagy confirmed by Western blot (PMC9827794); quercetin inducing apoptosis in AML cells through downregulation of VEGF/Akt signaling with mitochondria-mediated apoptosis confirmed (PMC7758733); and quercetin targeting epigenetic regulators in HL-60 and U937 AML cell lines through DNMT1/DNMT3a elimination and HDAC downregulation inducing demethylation of pro-apoptotic BCL2L11, DAPK1, BAX, APAF1, BNIP3, and BNIP3L genes and confirmed in vivo xenograft activity (PMC6225654) — directly targeting the dominant epigenetic driver gene mutations (DNMT3A ~18-22%, TET2 ~7-23%, IDH1 ~7-12%, IDH2 ~10-15%) that are the most common category of AML mutations.
Plant-Based Description
Whole-food plant-based dietary patterns provide phytochemicals with documented direct anti-AML cell line activity across multiple published studies. Quercetin from onions, kale, and apples induced autophagy-associated cell death in HL-60 human AML cells through CaMKKbeta/AMPK/mTOR pathway — AMPK phosphorylation increase and mTOR phosphorylation decrease confirmed by Western blot, LC3-II ratio increase confirmed, Beclin-1 upregulation confirmed, and p62 downregulation confirmed in HL-60 and primary AML cells (PMC9827794); quercetin induced apoptosis in AML cells through VEGF/Akt signaling downregulation with MMP dissipation and mitochondria-mediated caspase cascade confirmed (PMC7758733); quercetin targeted epigenetic regulators in HL-60 and U937 AML cell lines eliminating DNMT1 and DNMT3a expression, downregulating class I HDACs, demethylating BCL2L11, DAPK1, BAX, APAF1, BNIP3, and BNIP3L pro-apoptotic gene promoters confirmed (PMC6225654) targeting the dominant DNMT3A/TET2/IDH1/IDH2 epigenetic driver mutations in AML (~60-70% of AML cases); curcumin induces apoptosis and inhibits NF-kB in AML cell models; EGCG inhibits FLT3-ITD downstream STAT5/PI3K/AKT and activates p53 in AML cell models; resveratrol inhibits NF-kB, activates SIRT1, and induces differentiation in AML cell models.
Plant Chemistry Detail
Quercetin from onions, kale, and apples has the most comprehensively documented anti-AML cell line activity across three confirmed published studies targeting the dominant molecular pathways in AML.
In the first study (PMC9827794) using HL-60 human AML cells: phosphorylated AMPK (p-AMPK) protein expression was lower in primary AML cells, HL-60 cells, KG-1, and THP-1 AML cells than in peripheral blood mononuclear cells; after quercetin treatment, p-AMPK expression increased while p-mTOR expression decreased in a dose-dependent manner confirmed by Western blot; quercetin induced apoptosis confirmed; quercetin induced autophagic cell death in HL-60 cells with LC3 II/I ratio increase, Beclin-1 upregulation, and p62 downregulation confirmed; CaMKKbeta siRNA silencing reduced quercetin-activated AMPK phosphorylation demonstrating the CaMKKbeta-AMPK-mTOR mechanism; this directly targets the FLT3-ITD/mTORC1-driven autophagy suppression documented in AML.
In the second study (PMC7758733) using AML cells: quercetin induced apoptosis via downregulation of VEGF/Akt signaling pathway; quercetin decreased mitochondrial membrane potential (MMP) in AML cells; the decrease of MMP and cell death was rescued by PI3K/Akt activator confirming VEGFR2 and PI3K/Akt as upstream regulators of quercetin's apoptosis induction mechanism; quercetin-induced apoptosis used the mitochondria-mediated caspase cascade directly targeting the VEGF/PI3K/AKT/mTOR anti-apoptotic signaling pathway constitutively active in AML through FLT3-ITD (~25-28% of AML), NRAS/KRAS (~15% combined), and PTEN loss.
In the third study (PMC6225654) using HL-60 and U937 human AML cell lines with in vivo xenograft validation: quercetin almost eliminated DNMT1 and DNMT3a expression in AML cell lines confirmed by Western blot — directly targeting DNMT3A R882H mutations (~18-22% of AML) and DNMT3a-dependent epigenetic silencing; quercetin downregulated class I HDACs through increased proteasome degradation confirmed by MG132 proteasome inhibitor experiment; quercetin induced demethylation of pro-apoptotic BCL2L11 (BIM encoding gene), DAPK1, BAX, APAF1, BNIP3, and BNIP3L gene promoters in a dose- and time-dependent manner confirmed; quercetin treatment for 48 hours caused accumulation of acetylated histone H3 and H4 with 3 to 10-fold increases in promoter regions of DAPK1, BCL2L11, BAX, APAF1, BNIP3, and BNIP3L; quercetin showed in vivo activity in two human xenograft AML models directly targeting the epigenetic silencing of pro-apoptotic genes driven by the dominant AML epigenetic driver mutations.
Quercetin additionally induced PARP cleavage in THP-1, MV4-11, and U937 AML cell lines; caused DNA fragmentation and G2/M cell cycle arrest in U937 AML cells; induced upregulation of pro-apoptotic Bax and suppression of anti-apoptotic BCL2, BCL-xL, and MCL-1 in AML cell lines (PMC8510366). Curcumin inhibits NF-kB, activates apoptosis, and inhibits DNMT targeting the dominant epigenetic mutations and the NF-kB pathway in AML. EGCG from green tea inhibits FLT3-ITD downstream STAT5 phosphorylation and PI3K/AKT/mTOR in AML cell models, activates p53, and inhibits DNMT targeting epigenetic gene silencing. Genistein from soybeans inhibits NF-kB, PI3K/AKT, and induces differentiation in AML cell models. Apigenin from parsley induces apoptosis in HL-60 and U937 AML cells through caspase-3 activation and Bcl-2 reduction in published research. Fisetin from strawberries induces apoptosis and cell cycle arrest in AML cell models through PI3K/AKT/mTOR inhibition. Resveratrol inhibits NF-kB and FLT3 downstream signaling in AML. Allicin from garlic induces apoptosis in HL-60 AML cells through ROS generation and caspase-3 activation in published research.
Nutritional Focus
Nutritional focus in acute myeloid leukemia research is led by quercetin from onions, kale, and apples with directly documented anti-AML cell line activity targeting the dominant molecular pathways in AML across three confirmed published studies: quercetin inducing autophagy-associated cell death in HL-60 human AML cells through CaMKKbeta/AMPK/mTOR pathway with dose-dependent p-AMPK increase and p-mTOR decrease, LC3-II autophagy confirmation, Beclin-1 upregulation, and p62 downregulation confirmed in HL-60 and primary AML cells (PMC9827794) directly targeting FLT3-ITD/mTORC1-driven autophagy suppression (~25-28% of AML); quercetin inducing apoptosis in AML cells through VEGF/Akt signaling downregulation with MMP dissipation and PI3K/Akt rescue experiment confirming mechanism (PMC7758733); quercetin eliminating DNMT1 and DNMT3a expression, downregulating class I HDACs, demethylating BCL2L11, DAPK1, BAX, APAF1, BNIP3, and BNIP3L pro-apoptotic gene promoters with acetylated H3 and H4 accumulation confirmed in HL-60 and U937 AML cells with in vivo xenograft validation (PMC6225654) directly targeting the dominant DNMT3A (~18-22% of AML), TET2 (~7-23%), IDH1 (~7-12%), and IDH2 (~10-15%) epigenetic driver mutations that collectively occur in approximately 60 to 70 percent of all AML cases; additionally quercetin inducing PARP cleavage in THP-1, MV4-11, and U937 AML cell lines and causing G2/M arrest in U937 cells and upregulating Bax while suppressing BCL2/BCL-xL/MCL-1 (PMC8510366); curcumin inhibiting NF-kB and targeting DNMT targeting the dominant epigenetic landscape; EGCG from green tea inhibiting FLT3-ITD downstream STAT5 and PI3K/AKT/mTOR and activating p53; apigenin from parsley inducing apoptosis in HL-60 and U937 AML cells through caspase-3 activation and Bcl-2 reduction; allicin from garlic inducing apoptosis in HL-60 AML cells through ROS generation and caspase-3 activation; and beta-glucans from whole mushrooms and grains modulating innate immune NK cell and macrophage anti-AML surveillance through TLR/dectin-1 receptor signaling confirmed in published research.
Research Notes
AML epidemiology: US ~20,800 new cases and ~11,220 deaths projected 2024; ~1.1% of all US cancer diagnoses; globally ~119,000 new cases and ~98,000 deaths annually (GLOBOCAN 2022); most common acute leukemia in adults (~80% of adult acute leukemias); median age at diagnosis ~68 years; 5-year OS all ages ~29-32%; 5-year OS younger adults favorable risk ~50-70%; 5-year OS older adults (>70 years) ~5-10%. Molecular alterations: NPM1 mutations ~28-32% (most common, exon 12 type A insertion, favorable when FLT3-ITD-low); FLT3-ITD ~25-28% (adverse); FLT3-TKD ~7-8% (intermediate); DNMT3A ~18-22% (R882H hotspot, adverse); IDH1 ~7-12% (R132H); IDH2 ~10-15% (R140Q/R172K); TET2 ~7-23%; RUNX1 ~10% (adverse); ASXL1 ~5-11% (adverse); CEBPA biallelic ~6-10% (favorable); TP53 ~8-14% (biallelic adverse, complex karyotype); NRAS ~10%; KRAS ~5%; KIT ~4-5% (25-30% in CBF-AML); EZH2 ~2-5%; SRSF2/SF3B1/U2AF1 splicing ~15-20% (AML-MR); STAG2/cohesin ~5-10%. ELN 2022 risk groups: favorable (~15-25%), intermediate (~25-35%), adverse (~40-50%). Quercetin HL-60 AML (PMC9827794): CaMKKbeta/AMPK/mTOR; p-AMPK increase/p-mTOR decrease Western blot; LC3-II autophagy; Beclin-1 up/p62 down; primary AML cells confirmed. Quercetin AML VEGF/Akt (PMC7758733): MMP dissipation; PI3K/Akt activator rescue confirmed mechanism. Quercetin epigenetic HL-60 U937 xenograft (PMC6225654): DNMT1/DNMT3a elimination; HDAC downregulation; BCL2L11/DAPK1/BAX/APAF1/BNIP3/BNIP3L demethylation; acetylated H3/H4 accumulation 3-10-fold; in vivo xenograft two models. Quercetin THP-1 MV4-11 U937 (PMC8510366): PARP cleavage; G2/M arrest; Bax up/BCL2/BCL-xL/MCL-1 down.
Notes Visibility
show
Key Foods
Turmeric,Broccoli,Kale,Spinach,Brussels Sprouts,Cauliflower,Garlic,Yellow Onion,Carrot,Tomato,Beetroot,Cabbage,Blueberry,Pomegranate,Grape,Raspberry,Strawberry,Apple,Orange,Lemon,Soybeans,Edamame,Green Lentils,Black Beans,Chickpeas,Brown Rice,Quinoa,Oats,Wild Rice,Black Rice,Walnut,Almond,Brazil Nut,Flaxseed,Pumpkin Seeds,Chia Seeds,Sesame Seeds,Hemp Seeds,Shiitake,Maitake,Cremini,Portobello,Lions Mane,Green Tea,Ginger,Black Pepper,Garlic Powder,Parsley,Rosemary,Oregano, Celery, Leek,Avocado,Artichoke,Endive,Radish,Parsnip,Radicchio,Fig,Tangerine,Dragon Fruit Red, Red Onion
Linked Nutrients
vitamin-c,vitamin-e,vitamin-d3,vitamin-b9,vitamin-b6,vitamin-a,selenium,zinc,magnesium,calcium,potassium,iron,quercetin,curcumin,egcg,apigenin,resveratrol,genistein,beta-carotene,anthocyanins,beta-glucans,dietary-fiber
