Chronic Myelomonocytic Leukemia (CMML)
What is chronic myelomonocytic leukemia ?
Chronic myelomonocytic leukemia (CMML) is a rare, slowly progressing blood cancer. “Myelo-” means “marrow,” referring to the bone marrow.
A stem cell (blood-producing cell) in the bone marrow mutates (changes). These changes happen after conception, meaning these mutations are not passed down from your parents.
The change in the stem cell causes it to make too many blasts and monocytes. Blasts are immature blood cells that can become either red blood cells or different types of white blood cells. Monocytes are the largest white blood cells in the blood that fight infections. “Mono-” means one, and “cyte” means cell.
Monocytes take up a lot of space in the bone marrow. The bone marrow struggles to make other blood cells (red blood cells, platelets, and other white blood cells). – Leukemia Research Foundation
Conventional Treatments
Source: National Cancer Institute
- Hydroxyurea (chemo drug)
- Hypomethylating agents
- Allogeneic stem cell transplant (SCT)
Patients with high-risk disease who are young enough and fit enough may undergo allogeneic SCT. This represents the only potential cure for CMML.
A retrospective review of 1,114 patients with CMML diagnosed between 2000 and 2014 included 384 patients who underwent allogeneic SCT.[29] With a median follow-up of 51 to 78 months (in two data sets), allogeneic SCT in patients with low-risk CMML was detrimental, with a 5-year OS rates of 20% for patients who underwent allogeneic SCT and 42% for patients who did not undergo allogeneic SCT
For patients with high-risk CMML, there was no statistically significant difference in 5-year OS rates among patients treated with or without allogeneic SCT (27% vs. 15%, respectively).
For full details about above treatments see National Cancer Institute.
Types of chronic myelomonocytic leukemia
Source: Leukemia Research Foundation
The WHO classifies CMML into two subtypes based on the number of white blood cells in the blood.
- Myelodysplastic CMML (MD-CMML): There are less than 13,000 white blood cells/µL in the blood.
- Myeloproliferative CMML (MP-CMML): There are 13,000 or more white blood cells/µL in the blood.
Key mutations in CMML
TET2, ASXL1, SRSF2, DNMT3A, SF3B1, NRAS/KRAS
CBL, JAK2, V617F, RUNX1, SETBP1, TP53
Compounds that exert influence on the mutations listed above.
Evidence level summary
Strongest preclinical support (cell/animal): curcumin, quercetin, EGCG, berberine, sulforaphane, resveratrol, boswellia (AKBA). PMC+4PMC+4PMC+4
Clinical human data in leukemia/CMML: extremely limited. Most supportive data are preclinical or from non-hematologic cancers. Where human trials exist (eg. curcumin, green tea polyphenols), they are small, often in solid tumors, and use varying formulations.
Most are available as Extracts.
- EGCG (Green tea) (Epigallocatechin gallate)
Dosage: 400–800 mg/day (decaf form) - Curcumin Use turmeric liberally with black pepper
Dosage: 2–6 g/day oral - Quercetin
Dosage: 500–1500 mg/day - Boswellia Extract Powder 30% AKBA
Dosage: 300–500 mg 2–3×/day - Berberine
- Dosage: 500 mg 2–3×/day
- Sulphoraphanes (Broccoli Sprouts, Cauliflower)
Dosage: 20–40 mg/day (sulforaphane equivalent - Resveratrol (Grapes, berries, red wine)
Dosage: 500–1000 mg/day - Omega 3 (Fatty fish, fish oil supplements)
Dosage: 2–4 g/day combined - Rosemary
Dosage: 200–500 mg/day extract. Culinary: 2–5 g dried leaf daily. - Sage
Dosage: Tea (infusion): 2–3 cups/day, each from ~1–2 g dried leaf.
Extracts: 300–600 mg/day - Curcumin & Resveratrol
Dosage: Curcumin 2–6 g/day oral / Resveratrol 500–1000 mg/day - Aged Garlic / raw garlic
Dosage: typical trial range 1–2.4 g/day - Honokiol
- Dosage: 200–500 mg/day
- Methyl donors (B12, Folate, Choline)
Dosage: Standard RDA unless deficient - Vitamin D3
Dosage: Dose to maintain 40–60 ng/mL (check 25(OH)D) - Vitamin A (Retinoids)
Dosage: Diet-level or low-dose under guidance - Fisetin (Strawberries, Apples, and Onions)
Dosage: 500–1000 mg/day, 2–3×/week (senolytic cycles) - Melatonin
Dosage: 3–10 mg nightly - Olive oil (Oleuropein)
Dosage: 80–100 mg/day (extract) - Quercetin + Fisetin (senolytic combo)
Dosage: Quercetin 1–2 g/day + Fisetin cycles
Prescription only: - Metformin (Drug used to control glucose in your blood)
Dosage: 500–1000 mg/day (or as prescribed).
These don’t “cure” CMML but aim to modulate the terrain so abnormal clones are less advantaged.
Metabolic stabilizers: intermittent fasting, calorie restriction mimetics (e.g. spermidine) reduce oxidative stress and inflammatory cytokines.
PROBIOTICS
(L. reuteri, L. brevis) linked with immune regulation and may influence epigenetic methylation.
Many CMML patients on forums report lower inflammation markers and steadier blood counts when combining these approaches, though not reversal of disease.
Important
- Evidence. None of the compounds listed below have been proven to reverse or slow disease progression in CMML patients. They have shown some ability in cell culture or animal models to target some of the things that drive the disease and may help to at least slow disease progression.
- Dosages are anecdotal ranges (from patient forums, integrative oncology clinics, and supplement trials in other cancers, not PCMML-specific).
- Bioavailability is a recurring problem (curcumin, resveratrol, EGCG). High oral doses may be needed to reach target concentrations in marrow — formulations (nanoparticles, phytosome, etc.) improve this but are experimental. PMC
- Quality & purity: supplements vary widely — use pharmacopeial/third-party tested sources if a clinician agrees to trial them.
- Interactions with chemotherapy, targeted agents, or transplant — many botanicals alter drug-metabolizing enzymes, anticoagulation, or marrow recovery. Do not combine without provider approval.
- Antioxidants (e.g., NAC, high oral vitamin C) can be protective for normal cells but sometimes protect malignant clones — effects differ by model. PMC+1
- “Natural” ≠ “safe for cancer” — natural compounds can be potent and have serious effects.
- Effects vary wildly from person to person.
- Interactions are real: many of these compounds alter liver enzymes (CYP450), platelet function, or drug absorption.
- With weekly CBCs, you may see effects on WBCs, platelets, liver function — but it’s essential your doctor knows what you’re trialing.
- Pick 1–2 interventions per category (don’t start all at once).
- Track WBC, neutrophils, monocytes, CRP, and symptoms (fatigue, spleen size, night sweats).
- If a supplement correlates with WBC drop or cytokine improvement, continue;
if counts destabilize or toxicity appears, stop.
Supporting Evidence
Compounds
CURCUMIN
Dietary Source: Turmeric
Targets Epigenetic regulators (TET2, ASXL1, DNMT3A, EZH2, IDH1/2)
Signaling / RAS pathway (NRAS, KRAS, CBL, JAK2, PTPN11)
Cytokine / Growth factor excess (GM-CSF, IL-6, IL-8, TNF-α, VEGF, etc.)
Studies In vitro & animal studies show reduced GM-CSF and lower Th17/GM-CSF cytokines; some human anti-inflammatory trials (nanocurcumin) exist. ScienceDirect
Curcumin (turmeric extract) — modulates MAPK, PI3K/Akt/mTOR and downstream survival signals; induces apoptosis in multiple cancer cell lines.
Evidence: many cell/animal studies and reviews. PMC
Caution: poor oral bioavailability unless formulated; may interact with some chemo drugs and anticoagulants.
Curcumin & quercetin — reported in reviews to reduce expression or phosphorylation of key glycolysis regulators via PI3K/Akt/mTOR inhibition. BioMed Central
Curcumin, resveratrol — reported to influence HDACs, DNMTs and related chromatin modifiers in lab studies. BioMed Central
QUERCETIN
Dietary Source: Many fruits/vegetables (onions, apples, capers); parsley/celery have apigenin more.
RNA splicing (SRSF2, SF3B1, U2AF1)
Studies In vitro studies show suppression of GM-CSF production from stimulated immune cells; broad anti-inflammatory effects in animal models. PMC
Quercetin (flavonoid) — reported to downregulate PI3K/Akt and MAPK signaling and induce apoptosis in leukemia and other cancer cells. Evidence: in vitro and some animal studies; mechanistic reviews. PMC
Quercetin, curcumin — reported to influence mitochondrial apoptotic pathways and mitochondrial function in cancer cells. Frontiers
GREEN TEA ( EGCG )
Dietary Source: Green tea
Targets Epigenetic regulators (TET2, ASXL1, DNMT3A, EZH2, IDH1/2)
Cytokine / Growth factor excess (GM-CSF, IL-6, IL-8, TNF-α, VEGF, etc.)
Studies In vitro / animal studies show EGCG suppresses inflammatory signaling and can reduce cytokine/STAT activation related to GM-CSF pathways. PMC
EGCG (epigallocatechin-3-gallate, green tea catechin) — inhibits PI3K/Akt/mTOR and other pro-survival pathways; reported to reduce glycolytic signaling in cancer models. Evidence: robust preclinical literature and reviews. PMC
EGCG (green tea) — reported to inhibit glycolytic enzymes and PI3K-mediated glycolytic signaling; reduces glucose uptake in models. Frontiers
BERBERINE
Targets Signaling / RAS pathway (NRAS, KRAS, CBL, JAK2, PTPN1
Berberine — several studies show berberine can suppress glutamine uptake (SLC1A5) and inhibit mitochondrial respiration in cancer cells; reported antitumor activity in vitro and in vivo. Evidence: preclinical studies showing reduced glutamine transport and mitochondrial effects. PMC
Berberine — inhibits mitochondrial respiration and ATP production in tumor cells (oncosis/mitochondrial dysfunction reported). ScienceDirect
SULFORAPHANE
Dietary Source: Broccoli sprouts (3-day-old – eaten raw or lightly steamed)
Targets RNA splicing (SRSF2, SF3B1, U2AF1) Transcription factors (RUNX1, ETV6, NPM1)Stem-cell markers (CD34+, CD123, CD133, CD44, CD47, CXCR4)
Study Macrophages, mouse inflammation models. Inhibited NLRP3 activation; reduced IL-1β secretion and systemic inflammation PMID 28757246
Sulforaphane (broccoli sprouts / cruciferous vegetables) — strongly studied for epigenetic modulation (histone & DNA methylation effects) and reported activity against leukemia stem-like cells in preclinical models. Evidence: multiple preclinical reviews and leukemia-model studies. PMC+ ScienceDirect
RESVERATROL
Dietary Source: Grapes, berries, red wine
Targets Epigenetic regulators (TET2, ASXL1, DNMT3A, EZH2, IDH1/2)
Studies Cell and animal studies + reviews show resveratrol can decrease GM-CSF production in inflammatory models. PMC
Resveratrol — modulates AMPK/SIRT1 and can downregulate PI3K/Akt in some leukemia models; induces apoptosis/autophagy in CML/other myeloid cell lines.
Evidence: preclinical studies; limited human data. AACR Journals
CURCUMIN + RESVERATROL
Targets Stem-cell markers (CD34+, CD123, CD133, CD44, CD47, CXCR4) ScienceDirect
BOSWELLIA EXTRACT POWDER 30% AKBA
(Acetyl 11-keto-β-boswellic acid (AKBA) is a potent anti-inflammatory agent obtained from oleo gum resin of Boswellic serrata. )
Targets Signaling / RAS pathway (NRAS, KRAS, CBL, JAK2, PTPN11)
Cytokine / Growth factor excess (GM-CSF, IL-6, IL-8, TNF-α, VEGF, etc.)
Boswellia (AKBA — acetyl-11-keto-β-boswellic acid) — anti-inflammatory and NF-κB inhibition; some studies show antiproliferative effects and interaction with survival pathways. Evidence: preclinical/cell studies and extracts used as anti-inflammatory supplements. PMC
OMEGA-3 (EPA/DHA)
Dietary Source: Fatty fish, fish oil supplements
Targets RNA splicing (SRSF2, SF3B1, U2AF1)
Cytokine / Growth factor excess (GM-CSF, IL-6, IL-8, TNF-α, VEGF, etc.)
Stem-cell markers (CD34+, CD123, CD133, CD44, CD47, CXCR4)
Studies Multiple human and animal studies report reductions in pro-inflammatory cytokines including GM-CSF in some settings (biomarker studies). PMC
ROSEMARY and SAGE
Reduces inflammatory cytokines and modulate pathways relevant to GM-CSF
Studies In vitro and animal inflammation/neuro models show carnosic acid/carnosol reduce inflammatory cytokines and modulate pathways relevant to GM-CSF. Recent papers highlight anti-inflammatory potential. PMC
AGED GARLIC / RAW GARLIC
Dietary Source: (1–2 raw cloves/day or 1–1.2 g/day aged extract)
Targets Suppression of Ras pathway
Study Cell and animal models (oncology, not CMML). Reported nonspecific FTI activity and suppression of Ras pathway signaling in preclinical models. PMID: 16278491
HONOKIOL
Dietary Source: Magnolia bark – Available as supplement.
Has Anti-leukemic activity. Study: AML cell lines and primary samples. Suppressed constitutive/inducible STAT3 signaling in AML; anti-leukemic activity. ScienceDirect
METHYL DONORS
Dietary Source: B12, Folate, Choline
Targets Epigenetic regulators (TET2, ASXL1, DNMT3A, EZH2, IDH1/2) PMC
VITAMIN B3
Targets Transcription factors (RUNX1, ETV6, NPM1) ScienceDirect
VITAMIN A (Retinoids)
Targets Transcription factors (RUNX1, ETV6, NPM1) ScienceDirect
OLIVE OIL(Oleuropein)
Targets Disrupts S100A9 amyloid assemblies ScienceDirect
FISETIN
Dietary source: Strawberries, Apples, and Onions
Targets Cohesin & SETBP1 PMC
MELATONIN
Targets Cohesin & SETBP1
Melatonin — modulates mitochondrial function, ROS, and some signaling pathways; limited leukemia data. ScienceDirect
METFORMIN (Drug used to control glucose in your blood)
Targets Signaling / RAS pathway (NRAS, KRAS, CBL, JAK2, PTPN11) SpandidosPublications
Frequency of somatic mutations in patients with CMML.
| Major class of genetic mutation Gene | Frequency of mutation |
| Epigenetic control | |
| Histone modification ASXL1a EZH | 40% 2 5% |
| DNA methylation TET2 DNMT3Aa | 60% 5% |
| Dual effect IDH1 IDH2 | 1% 5%-10% |
| Cell signaling JAK2V617F CBL NRASa KRAS PTPN11 FLT3 | 5%-10% 15% 15% 10% 5% <5% |
| Pre-mRNA splicing SRSF2 SF3B1 U2AF1 ZRSR2 | 50% 5%-10% 5%-10% 5% |
| Transcription and nucleosome assembly RUNX1a SETBP1a | 15% 15% |
| DNA damage TP53 PHF6 | 1% 5% |
Source: Patnaik MM, Tefferi A. Chronic myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management. American Journal of Hematology. 2020;95:97-115.