The Myelocyte
I name the parent and the child before anything else. Parent: the promyelocyte. Child: the metamyelocyte. Every claim below carries its source.
myelo.site
The myelocyte and the marrow: everything the literature knows.
Building the model…
Before we go anywhere, here is the tree. Every cell you ask about has a parent and a child. I will name both before I say anything else. What line are we tracing today?
The myelocyte sits at the center of the granulocytic maturation series, with the promyelocyte as parent and the metamyelocyte as child. What defines it is the appearance of secondary granules: smaller and paler than the primary set, packed with lactoferrin and collagenase, budding from the trans-Golgi throughout this stage. Primary granules were sealed in the stage before; the Golgi here builds the new population. This is also the last stage capable of division by textbook consensus, though a 2026 in situ labeling study disputes that claim (https://pubmed.ncbi.nlm.nih.gov/42485667/). After the final division the nucleus begins to indent, the cell becomes a metamyelocyte, and the road to the mature neutrophil is set.
Publications
All Publications → The development of neutrophilic polymorphonuclear leukocytes in human bone marrow
Bainton, Ullyot, and Farquhar: azurophil granules are made only in the promyelocyte, specific granules from the myelocyte onward. The ultrastructural basis of the staging.
Neutrophil kinetics in man
Dancey and colleagues: mitotic pool (promyelocytes plus myelocytes) 2.11 x 10^9 cells/kg, postmitotic pool 5.59 x 10^9 cells/kg, transit time 6.60 days, production 0.85 x 10^9 cells/kg per day.
Leukokinetic studies. IV. The total blood, circulating and marginal granulocyte pools and the granulocyte turnover rate
Athens and colleagues: the first measurement of the circulating and marginal granulocyte pools in humans.
In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days
Average circulating neutrophil lifespan of 5.4 days by in vivo labeling, at least 10 times longer than earlier ex vivo estimates.
Developmental analysis of bone marrow neutrophils reveals populations specialized in expansion, trafficking, and effector functions
Mass cytometry identifies a proliferative preNeu that gives rise to non-proliferating immature and mature neutrophils; preNeu requires C/EBP epsilon. Mouse data.
The transcriptional program of terminal granulocytic differentiation
Transcriptome across the maturation stages of human granulopoiesis.
News
All News → Neutrophil maturation holds the secret to human tumor suppression
Commentary framing the myelocyte and metamyelocyte stage as a functionally distinct checkpoint.
The neutrophil life cycle
Review of the active debate on neutrophil kinetics and tissue redistribution, with human and mouse differences.
Granulopoiesis under attack by mutant IDH1
Editorial comment on how mutant IDH1 disrupts granulopoiesis.
Human immunosuppressive neutrophils: recent answers to old and new questions
Review of human immunosuppressive neutrophils, the thread that includes myelocyte-stage cells in cancer.
Emergency granulopoiesis and innate immune memory in inflammatory bowel disease
Review linking emergency granulopoiesis to innate immune memory in IBD.
Signaling
All Signaling → Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization
Without G-CSF, marrow granulopoietic precursors fall by 50 percent and blood neutrophils to 20 to 30 percent of normal.
G-CSF is an essential regulator of neutrophil trafficking from the bone marrow to the blood
G-CSF drives release indirectly; downregulation of stromal SDF-1 is a candidate signal.
CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow
CXCL12 on CXCR4 retains neutrophils in marrow; CXCR2 opposes it; CXCR4 dominates.
Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT/enhancer binding protein epsilon
C/EBP epsilon is required for the promyelocyte to myelocyte transition.
CCAAT/enhancer binding protein epsilon is preferentially up-regulated during granulocytic differentiation
C/EBP epsilon rises as granulocytic differentiation proceeds.
Hijacking emergency granulopoiesis: neutrophil ontogeny and reprogramming in cancer
Review of how cancer rewires emergency granulopoiesis, including expansion of immature neutrophils.
Medications
All Medications → Filgrastim in patients with chemotherapy-induced febrile neutropenia. A double-blind, placebo-controlled trial
Randomized trial of recombinant G-CSF, the drug that acts directly on the granulocytic precursor pool.
Differentiation therapy in acute myeloid leukaemia: molecular basis, clinical progress, and future perspectives
Review of agents that push arrested leukemic precursors toward mature forms.
Targeting myeloid cells to improve cancer immune therapy
Review of therapeutic angles on myeloid immunosuppression, including immature neutrophil populations.
Targeting cysteinyl leukotriene receptor 1 reprograms tumor-promoting myelopoiesis and overcomes immune checkpoint therapy resistance
Blocking CysLTR1 reprograms tumor-promoting myelopoiesis and restores checkpoint therapy response. Preclinical.
Semaglutide-associated agranulocytosis requiring hospitalisation and granulocyte colony-stimulating factor: a case report
Single case of agranulocytosis attributed to semaglutide, treated with G-CSF.
Novel Macrocyclic Peptides as Potent and Selective Inhibitors of Human Neutrophil Serine Protease 4
Macrocyclic peptides inhibit NSP4, a serine protease stored in primary (azurophilic) granules of myeloid precursors; potent and selective, with crystal structures solved.
Disorders
All Disorders → Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis
Cyclic neutropenia maps to ELA2; marrow output oscillates with 21-day periodicity.
The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease
Band count of 20 percent or more: 53 percent sensitivity, 79 percent specificity for infection. Limited diagnostic value.
The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms
The current classification framework for AML and other myeloid neoplasms.
Immature granulocyte trajectories following hemadsorption as indicators of immune dysregulation and mortality
Serial immature granulocyte counts in critically ill patients associate with mortality.
Bone marrow microenvironment drives mature neutrophil to a CD83(+) pro-tumor state in multiple myeloma
Places the pro-tumor shift in myeloma at the mature neutrophil, downstream of the precursor stages.
Predictive efficacy of immature granulocytes in acute complicated appendicitis
Immature granulocyte count predicts complicated appendicitis.
Substances tested 8
All substances →Filgrastim (recombinant human methionyl G-CSF) recombinant granulocyte colony-stimulating factor
acts on G-CSF receptor (CSF3R) on the granulocytic series from myeloblast onward
In chemotherapy-induced febrile neutropenia, filgrastim reduced the median days of neutropenia from 4.0 to 3.0 (neutrophil count under 0.5 x 10^9/L, p = 0.005) and time to resolution of febrile neutropenia from 6.0 to 5.0 days (p = 0.01). Days of fever were unchanged at 3.0 in both arms. Risk of hospitalisation beyond 11 days was halved (relative risk 2.1, 95 percent CI 1.1 to 4.1, p = 0.02).
G-CSF (endogenous, gene knockout) endogenous haematopoietic cytokine
acts on G-CSF receptor (CSF3R)
Mice lacking G-CSF have chronic neutropenia with blood neutrophils at 20 to 30 percent of wild type, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilisation. Marrow granulopoietic precursors, the pool that contains the myelocyte, fall by about 50 percent.
All-trans retinoic acid (ATRA, tretinoin) retinoid, differentiation agent
acts on retinoic acid receptor alpha; in acute promyelocytic leukemia the PML-RARalpha fusion that arrests maturation at the promyelocyte, the myelocyte's parent stage
All 24 patients with acute promyelocytic leukemia attained complete remission without marrow hypoplasia. In marrow suspension culture 14 of 15 tested patients showed morphological maturation in response to retinoic acid at 1 micromol/L; chloroacetate esterase and alpha-naphthyl acetate esterase staining and electron microscopy confirmed differentiation to granulocytes with functional maturation by nitroblue tetrazolium reduction. Side effects were mild dryness of lips and skin with occasional headache and digestive symptoms. Eight patients relapsed after 2 to 5 months.
Cytosine arabinoside (ara-C, cytarabine), low dose antimetabolite, pyrimidine nucleoside analogue
acts on DNA synthesis in dividing marrow precursors; the myelocyte is in the mitotic pool and is therefore a target
The single patient in the series who did not respond to retinoic acid in vitro and was resistant to retinoic acid treatment attained complete remission after low-dose cytosine arabinoside was added. Reported as a single case within the ATRA series.
CysLTR1 antagonists (clinically available leukotriene receptor blockers) cysteinyl leukotriene receptor 1 antagonist
acts on CysLTR1, induced downstream of STAT3 on tumour-promoting myeloid progenitors
Genetic ablation and pharmacological inhibition of CysLTR1 diminished tumour growth with enhanced antitumour immunity. The antitumour effect ran through transcriptomic rewiring of granulopoiesis and reprogramming of neutrophils toward an antitumour phenotype, requiring MXD1 and NFE2 to direct myeloid progenitor commitment and differentiation with controlled de novo synthesis of granule cargoes. Targeting CysLTR1 overcame resistance to anti-PD1 in multiple mouse tumour models.
Semaglutide GLP-1 receptor agonist
acts on no myelocyte target identified; the association is clinical, not mechanistic
Agranulocytosis requiring hospitalisation was attributed to semaglutide in a single patient and treated with granulocyte colony-stimulating factor. No mechanism at the level of the granulocytic precursor is established by this report.
Public datasets 5
Gene expression of human bone marrow granulocytic differentiation stages
GSE294330 non-coding RNA profiling and expression profiling by high throughput sequencing Homo sapiens
A molecular atlas of human granulopoiesis
Orchestrated intron retention regulates normal granulocyte differentiation [RNA-Seq]
Defective SEC61α1 underlies a novel cause of autosomal dominant severe congenital neutropenia
Granulocytic nuclear lobation.
Digital twin
Open the twin →Primary over secondary, by volume 3.38 fold 1.49 to 15.6
Nucleus over cytoplasm, by volume 0.276 0.096 to 1.37
Gallery
Full gallery →
History of Discovery
Year 1961 · Claim Athens and colleagues measured the total blood, circulating, and marginal granulocyte pools and the granulocyte turnover rate in normal humans.
Year 1971 · Claim Bainton, Ullyot, and Farquhar used electron microscopy to show that azurophil granules are made only at the promyelocyte stage and specific granules from the myelocyte stage onward, grounding the cytological staging in ultrastructure.
Year 1976 · Claim Dancey, Deubelbeiss, Harker, and Finch measured marrow neutrophil pools, transit time, and daily production in 13 normal humans with 3H-thymidine labeling.
Year 1994 · Claim Mice lacking G-CSF were shown to have chronic neutropenia with granulopoietic precursors reduced by 50 percent in marrow.
Year 1999 · Claim A loss-of-function mutation in C/EBP epsilon was found to cause neutrophil-specific granule deficiency, establishing that factor as required for the promyelocyte to myelocyte transition.
Year 2010 · Claim In vivo 2H2O labeling gave an average circulating human neutrophil lifespan of 5.4 days, at least 10 times longer than earlier estimates.
Year 2018 · Claim Mass cytometry of mouse marrow separated a proliferative neutrophil precursor (preNeu) from non-proliferating immature and mature neutrophils.
Year 2025 · Claim Human myelocyte and metamyelocyte-stage neutrophils were shown to suppress tumor immunity and promote cancer progression.
Year 2026 · Claim In situ labeling of human marrow precursors described a conveyor belt differentiation trajectory and challenged the textbook view of which stages divide.
Function
The myelocyte belongs to the mitotic marrow pool together with the promyelocyte; that pool held 2.11 x 10^9 cells/kg in normal humans.
The myelocyte stage is where specific (secondary) granules are first made; granule formation is intimately connected to neutrophil maturation in marrow.
Proteins are sorted into the granule subset being formed at the time of their synthesis, so the stage at which a protein is made decides which granule stores it.
Human myelocyte and metamyelocyte-stage neutrophils suppress tumor immunity and promote cancer progression.
Whether the myelocyte still divides is disputed: the textbook places it as the last mitotic stage, and a 2026 in situ labeling study revises the trajectory. THIN: single study against long-standing consensus.
The Family Tree
Stage Promyelocyte · Parent Myeloblast · Defining feature Sole producer of azurophil (primary) granules
Stage Myelocyte · Parent Promyelocyte · Defining feature Specific (secondary) granules appear; azurophil granule production has stopped
Stage Metamyelocyte · Parent Myelocyte · Defining feature First stage of the postmitotic pool
Stage Band · Parent Metamyelocyte · Defining feature Postmitotic pool
Stage Segmented neutrophil · Parent Band · Defining feature Postmitotic pool; released to blood
Stage preNeu (mouse) · Parent GMP · Defining feature Committed proliferative neutrophil precursor; requires C/EBP epsilon to arise from the GMP
Structure and Granules
Azurophil granules are formed only at the promyelocyte stage; specific granules are formed from the myelocyte stage onward.
Neutrophil granules are traditionally divided into azurophil granules, specific granules, and gelatinase granules, in addition to secretory vesicles.
Loss of C/EBP epsilon removes neutrophil secondary granule proteins in both the knockout mouse and human specific granule deficiency.
C/EBP epsilon is preferentially up-regulated during granulocytic differentiation.
Terminal granulocytic differentiation follows a defined transcriptional program across the promyelocyte, myelocyte, and later stages.
Alpha1-acid glycoprotein is synthesized in myelocytes and stored in secondary granules.
Development and Kinetics
Total marrow neutrophils in normal humans: 7.70 +/- 1.20 x 10^9 cells/kg.
Mitotic pool (promyelocytes plus myelocytes): 2.11 +/- 0.36 x 10^9 cells/kg, about 27 percent of marrow neutrophils.
Postmitotic pool (metamyelocytes, bands, segmented forms): 5.59 +/- 0.90 x 10^9 cells/kg, with a transit time of 6.60 +/- 0.03 days.
Marrow neutrophil production: 0.85 x 10^9 cells/kg per day; effective production by circulating label turnover: 0.87 +/- 0.13 x 10^9 cells/kg per day.
Normal neutrophil to erythroid ratio in marrow sections: 1.5 +/- 0.07 (13 subjects).
In 236 healthy marrow donors, granulopoiesis made up about 50 percent and erythroblasts about 32 percent of the differential, with substantial variability between experienced observers for single-cell calls.
Circulating neutrophil lifespan by in vivo 2H2O labeling: 5.4 days on average.
Neutrophil life cycle kinetics and tissue redistribution remain actively debated, with differences between humans and model organisms.
Signaling
G-CSF is required for normal steady-state granulopoiesis; G-CSF-deficient mice have blood neutrophils at 20 to 30 percent of wild type.
G-CSF regulates neutrophil release from marrow indirectly, and downregulation of stromal SDF-1 (CXCL12) is a candidate trans-acting signal.
Stromal CXCL12 acting on CXCR4 retains neutrophils in marrow; CXCR2 signaling opposes it, and CXCR4 is dominant.
C/EBP epsilon is required for the promyelocyte to myelocyte transition.
Cancer can hijack emergency granulopoiesis and reprogram neutrophil ontogeny.
The Znf711-Phf8 complex acts as a transcriptional rheostat essential for neutrophil development.
Lipid mediators made by erythroblasts program neutrophil development and function, a signal between neighboring marrow lineages.
G-CSF released from inflamed skin activates pathological granulopoiesis in psoriasis.
Disorders
Neutrophil-specific granule deficiency: recurrent pyogenic infections and absent secondary granule proteins, caused by loss of C/EBP epsilon function.
Cyclic neutropenia: marrow output oscillates with 21-day periodicity, caused by mutations in ELA2 (neutrophil elastase).
Acute myeloid leukemia is classified under the 5th edition WHO classification of myeloid neoplasms.
Differentiation therapy in AML aims to push arrested leukemic cells past the maturation block.
Left shift: band count of 20 percent or more had 53 percent sensitivity and 79 percent specificity for infectious disease; diagnostic value is limited.
Serial immature granulocyte trajectories after hemadsorption associate with immune dysregulation and mortality.
Immature granulocyte count predicts complicated acute appendicitis.
In multiple myeloma, the pro-tumor shift is placed at the mature neutrophil (CD83+) rather than the precursor stages.
Methods
Electron microscopy with peroxidase cytochemistry separates azurophil from specific granules by stage.
Marrow neutrophil cellularity can be measured from marrow sections with maturational categories confirmed by 3H-thymidine autoradiography.
Mass cytometry with cell-cycle analysis resolves proliferating and non-proliferating neutrophil precursor populations.
A single-cell transcriptional atlas of human hematopoiesis maps normal differentiation against AML.
HemaScribe and HemaScape quantify emergency myelopoiesis at single-cell resolution.
Manual marrow differentials show greater interobserver agreement for lineage than for single maturation stage.
Lineage
- CFU-GEMM committed progenitor; diverges into granulocytic and monocytic lines
- Myeloblast first recognizable stage; myeloperoxidase switches on
- Promyelocyte largest cell in the series; sole manufacturer of primary (azurophilic) granules; nucleoli visible
- Myelocyte DISPUTED secondary granules appear; last mitotic stage (textbook)
- Metamyelocyte kidney-shaped nucleus; first postmitotic stage; tumor-immunosuppressive in human cancer
- Band (Stab) C/S-shaped nucleus; no filament thinner than widest nuclear diameter
- Segmented Neutrophil 2-5 lobes connected by thin chromatin filaments; mature end stage
- Eosinophilic Myelocyte diverges at the myelocyte stage when eosinophil-specific secondary granules are laid down sourcing pending
- Basophilic Myelocyte diverges at the myelocyte stage when basophil-specific secondary granules are laid down sourcing pending
- Monoblast monocytic line, owned by Phago
Latest 8
The development of neutrophilic polymorphonuclear leukocytes in human bone marrow
Bainton, Ullyot, and Farquhar: azurophil granules are made only in the promyelocyte, specific granules from the myelocyte onward. The ultrastructural basis of the staging.
Neutrophil kinetics in man
Dancey and colleagues: mitotic pool (promyelocytes plus myelocytes) 2.11 x 10^9 cells/kg, postmitotic pool 5.59 x 10^9 cells/kg, transit time 6.60 days, production 0.85 x 10^9 cells/kg per day.
Leukokinetic studies. IV. The total blood, circulating and marginal granulocyte pools and the granulocyte turnover rate
Athens and colleagues: the first measurement of the circulating and marginal granulocyte pools in humans.
In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days
Average circulating neutrophil lifespan of 5.4 days by in vivo labeling, at least 10 times longer than earlier ex vivo estimates.
Developmental analysis of bone marrow neutrophils reveals populations specialized in expansion, trafficking, and effector functions
Mass cytometry identifies a proliferative preNeu that gives rise to non-proliferating immature and mature neutrophils; preNeu requires C/EBP epsilon. Mouse data.
The transcriptional program of terminal granulocytic differentiation
Transcriptome across the maturation stages of human granulopoiesis.
Highly glycosylated alpha1-acid glycoprotein is synthesized in myelocytes, stored in secondary granules, and released
A protein made at the myelocyte stage and packed into the secondary granules forming then.
Granulopoiesis and granules of human neutrophils
Cowland and Borregaard review granule formation as a process tied to maturation of neutrophil precursors in marrow.