Acute Myeloid Leukemia

Slide 1 · Acute Myeloid Leukemia

Pathogenesis • classification • morphology • clinical correlations

A molecularly heterogeneous myeloid malignancy

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Relate acquired driver lesions to myeloid differentiation arrest.

Use morphology and lineage markers to recognize AML.

Distinguish major genetic and differentiation-defined patterns.

Explain marrow failure, bleeding, infection and prognosis.

Slide 3 · Three major myeloid neoplasms

AML

Immature myeloid blasts accumulate.

Marrow failure dominates presentation.

Other myeloid neoplasms

MDS: Ineffective, dysplastic hematopoiesis.

MPN: Usually increased output of mature blood cells.

Slide 4 · Normal blood-cell production

HSC

Multipotent stem-cell reservoir

Progenitors

Commitment to myeloid lineages

Maturation

Acquisition of functional cell features

Output

Erythrocytes, leukocytes, platelets

Schematic: Regulated differentiation sustains peripheral blood counts.

Slide 5 · Defining lesion in AML

A neoplasm of hematopoietic progenitor cells.

Acquired oncogenic alterations impede myeloid differentiation.

Immature blasts expand and replace functional marrow.

The critical consequence is failure of normal hematopoiesis.

Slide 6 · From mutations to marrow failure

Driver alterations

Differentiation and growth programs deranged

Blast expansion

Immature myeloid cells accumulate

Marrow replacement

Normal precursors are suppressed

Cytopenias

Anemia, neutropenia, thrombocytopenia

Marrow failure can occur without marked peripheral leukocytosis.

Slide 7 · Marrow failure has three major clinical outputs

Red-cell deficit

Reduced oxygen-carrying capacity → fatigue and pallor.

Neutrophil deficit

Reduced innate defense → fever and bacterial/fungal infections.

Platelet deficit

Impaired hemostasis → petechiae and mucosal bleeding.

Disease-related coagulopathy

Particularly important in acute promyelocytic leukemia.

Slide 8 · Who develops AML?

Disease can arise at any age.

Incidence increases with age and peaks after 60 years.

The clinical background often correlates with the molecular genotype.

Age alone does not identify a genetic subtype.

Slide 9 · AML is genetically heterogeneous

Numerous different oncogenic lesions converge on the AML phenotype.

Different clones are defined by their lineage maturation and genetics.

Molecular testing is integral to classification and risk assessment.

Morphology alone cannot identify every important genotype.

Slide 10 · Four functional classes of AML drivers

Transcription factors

Disruption of lineage-specific maturation programs.

Growth signaling

Constitutive proliferation and survival signals.

Epigenetic regulation

Disturbed methylation, chromatin architecture and gene expression.

P53 pathway

Impaired genome surveillance; Often therapy-resistant disease.

Slide 11 · Differentiation arrest is the central mechanism

Normal progenitor

Can proliferate and mature

Differentiation block

Genetic lesions impair terminal maturation

Blast pool

Immature cells persist and accumulate

Failure to differentiate—not just rapid division—defines the phenotype.

Slide 12 · RUNX1 and CBFB normally cooperate

RUNX1

DNA-binding transcription-factor component

CBFB

Partner that forms a functional complex with RUNX1

RUNX1–CBFB complex

Regulates normal hematopoietic differentiation

T(8;21) or inv(16) disrupts the cooperative transcriptional program.

Slide 13 · T(8;21): A differentiation-blocking fusion

T(8;21)

Recurrent chromosomal rearrangement

RUNX1::RUNX1T1

Chimeric transcription regulator

Myeloid maturation

Interference with normal differentiation

Textbook associates this genetic class with favorable prognosis.

Slide 14 · Inv(16): Perturbed core-binding factor

Inv(16)

Recurrent chromosome 16 inversion

CBFB::MYH11

Fusion interferes with core-binding factor

AML phenotype

Myeloid and monocytic differentiation

Abnormal eosinophilic precursors may aid recognition.

Slide 15 · Core-binding factor AML: Two pathways

T(8;21)

RUNX1::RUNX1T1 fusion.

Often full spectrum of myeloid maturation.

Auer rods and abnormal granules may be conspicuous.

Inv(16)

CBFB::MYH11 fusion.

Myelocytic plus monocytic differentiation.

Abnormal eosinophil precursors may be present.

Slide 16 · APL: The PML::RARA fusion

T(15;17)

Chromosomal rearrangement

PML::RARA

Retinoic-acid receptor fusion

Differentiation arrest

Abnormal promyelocytes accumulate

A distinctive AML subtype with clinically important coagulopathy.

Slide 17 · Why retinoic acid and arsenic work in APL

The PML::RARA fusion interferes with granulocytic differentiation.

All-trans-retinoic acid targets the fusion-associated maturation block.

Arsenic trioxide also targets the oncogenic fusion pathway.

APL illustrates molecularly directed differentiation therapy.

Slide 18 · FLT3: Constitutive survival signaling

FLT3 lesion

Activating receptor tyrosine kinase mutation

Growth-like signals

Promotes proliferation and survival

Blast fitness

Cooperates with other leukemogenic lesions

FLT3 activation can coexist with PML::RARA in APL.

Slide 19 · Cooperating mutations in leukemogenesis

Differentiation lesion

Blocks progression toward mature myeloid cells.

May leave proliferation/survival drive insufficient alone.

Signaling lesion

Enhances growth-factor-like activity.

Fosters survival and expansion of arrested precursors.

Slide 20 · RAS-pathway dysregulation

Driver changes also affect genes in progrowth signaling pathways.

The RAS family is among the recurrently affected pathways.

Growth-pathway activation is not synonymous with myeloid identity.

Combined genetic events help explain AML’s biologic diversity.

Slide 21 · Epigenetic deregulation in AML

DNA methylation

Driver variants may disturb methylation programs.

Chromatin organization

Cohesin-family alterations affect three-dimensional genome architecture.

Histone programs

Epigenetic defects alter regulatory states.

Gene expression

The resulting transcriptional changes may support malignant phenotypes.

Slide 22 · IDH-mutant AML: An oncometabolite pathway

IDH1 or IDH2 mutation

Enzyme acquires altered catalytic activity

2-hydroxyglutarate

Abnormal oncometabolite accumulates

Epigenetic disruption

Changes regulatory state and differentiation

Targeted mutant-IDH inhibition can induce clinical responses.

Slide 23 · Cohesin alterations and chromatin topology

Cohesin proteins organize chromatin in three dimensions.

Some AML drivers affect members of the cohesin family.

Disturbed chromosome topology may alter gene expression.

The exact causal links between epigenetic changes and AML remain incompletely resolved.

Slide 24 · TP53-mutated AML: A recognizable pattern

Genome

Frequently associated with complex karyotypes.

Morphology

Marked dysplasia and sometimes erythroid differentiation.

Clinical setting

Often seen following DNA-damaging therapy.

Outcome

Particularly poor response to standard treatment.

Slide 25 · Not every mechanism is fully resolved

Genetic lesions can be classified by their known molecular functions.

The immediate consequences of some epigenetic disturbances remain uncertain.

Cooperating events differ across patients and AML subtypes.

Genotype–phenotype relationships are informative but not perfectly deterministic.

Slide 26 · Integrated model of AML biology

Differentiation defects

Fusion transcription factors impair maturation

Growth advantage

Signaling alterations promote survival and proliferation

Other driver programs

Epigenetic and p53 pathway dysfunction

Functional classes may cooperate within the same AML clone.

Slide 27 · Two complementary classification approaches

Genetically defined AML

Entity anchored by a defining cytogenetic or molecular aberration.

Often carries subtype-specific morphologic and prognostic clues.

Differentiation-defined AML

Entity categorized by its morphologic lineage maturation.

Used when specific defining genetic abnormalities are absent.

Slide 28 · Why genetic classification is essential

Morphologically similar AMLs may have different molecular drivers.

Genetics can distinguish biologically coherent subtypes.

Genotype influences prognosis and therapeutic choice.

An integrated report includes morphology, immunophenotype and genetics.

Slide 29 · Genetically defined AML: Core examples

Genetic lesion

Gene/fusion

Textbook pattern

t(8;21)

RUNX1::RUNX1T1

Maturing blasts; Auer rods

inv(16)

CBFB::MYH11

Myelomonocytic; abnormal eosinophils

t(15;17)

PML::RARA

Abnormal promyelocytes; DIC

11q23 rearrangement

KMT2A

Often monocytic differentiation

Slide 30 · T(8;21) AML: Distinctive morphology

A spectrum of myelocytic maturation may be apparent.

Abnormal cytoplasmic granules are described.

Auer rods are often readily identified.

Molecular confirmation distinguishes this entity from morphology-only lookalikes.

Slide 31 · Inv(16) AML: Eosinophilic clues

Blasts may show granulocytic and monocytic differentiation.

Abnormal eosinophilic precursors contain atypical basophilic granules.

This clue should prompt a search for CBFB::MYH11.

The characteristic genetics carry prognostic significance.

Slide 32 · APL: Morphologic and clinical coupling

Blast stage

Neoplastic promyelocytes are prominent.

Granularity

Often abundant, coarse azurophilic granules.

Auer rods

May be numerous or form bundles.

Clinical hazard

Disseminated intravascular coagulation is an urgent concern.

Slide 33 · KMT2A-rearranged AML

The rearrangement involves 11q23 and the KMT2A gene.

Many cases show monocytic differentiation.

Robbins groups this pattern among unfavorable-risk examples.

A history of topoisomerase II inhibitor exposure is relevant.

Slide 34 · NPM1-mutant AML

A genetically recognized subtype detected by molecular testing.

A normal-appearing karyotype does not exclude driver mutations.

Favorable outcomes in the overview table.

Actual risk assignment requires the complete genetic and clinical context.

Slide 35 · AML with myelodysplasia-related genetics

Chromosomes

Loss/deletion involving 5q or 7q may be seen.

Splicing

SRSF2, SF3B1, U2AF1 and ZRSR2 are listed.

Other drivers

ASXL1, EZH2, BCOR and STAG2 are listed.

Interpretation

Integrate the abnormalities with AML morphology and clinical background.

Slide 36 · A useful distinction: Genotype versus maturation

Genetically defined entity

RUNX1::RUNX1T1 and PML::RARA name molecular subtypes.

The genetic event is central to subtype recognition.

Differentiation-defined entity

Descriptions such as monocytic or megakaryocytic emphasize lineage features.

Lineage is established through morphology and markers.

Slide 37 · Differentiation-defined AML patterns

Pattern

Salient discriminating feature

Minimally differentiated

Myeloid lineage by antigen expression; MPO-negative

Without / with maturation

Limited blasts versus wider myelocytic maturation

Myelomonocytic / monocytic

Coexisting granulocytic/monocytic or predominant monocytic maturation

Erythroid / megakaryocytic

Erythroid phenotype or platelet-lineage antigens; fibrosis may occur

Slide 38 · AML, minimally differentiated

Morphology alone may be insufficient to establish myeloid lineage.

Myeloperoxidase staining may be negative.

Flow-cytometric identification of myeloid-associated antigens becomes essential.

Avoid calling lineage based on one nonspecific morphologic feature.

Slide 39 · AML without maturation

Blast predominance reflects marked arrest in differentiation.

Limited appearance of maturing granulocytic elements.

Myeloperoxidase can support a myeloid assignment.

Distinguish from minimally differentiated and acute lymphoblastic leukemia.

Slide 40 · AML with maturation

Granulocytic cells may span a wider differentiation spectrum.

Myeloblasts coexist with recognizable maturing forms.

Auer rods, when present, support myeloid lineage.

A defining genetic lesion still takes precedence when identified.

Slide 41 · Two mixed-lineage maturation patterns

Myelomonocytic AML

Both granulocytic and monocytic maturation are present.

Morphology should be integrated with appropriate lineage markers.

Monocytic AML

Monoblasts and promonocytes predominate.

Nonspecific esterase is a useful cytochemical correlate.

Slide 42 · Monocytic AML: Why sites of infiltration matter

Monocytic tumors may infiltrate the gingiva and skin.

Normal monocytes are physiologically capable of tissue extravasation.

Leukemia cutis and gingival enlargement may be clinical clues.

Monocytic features alone do not define a single genetic subtype.

Slide 43 · AML with erythroid differentiation

Some AMLs contain a conspicuous neoplastic erythroid component.

The erythroid phenotype may coexist with marked dysplasia.

TP53-pathway alterations are particularly associated with such cases.

Interpret lineage findings in the context of the full marrow and genetic results.

Slide 44 · AML with megakaryocytic differentiation

Blasts demonstrate megakaryocyte-lineage markers such as GPIIb/IIIa.

Marrow fibrosis can obscure simple aspirate-based assessment.

Fibrogenic cytokines released by leukemic cells contribute to fibrosis.

Its association with Down syndrome.

Slide 45 · Lineage-specific clues guide the laboratory

Myeloid

Azurophilic granules, Auer rods, myeloperoxidase.

Monocytic

Folded nuclei, monoblasts/promonocytes, nonspecific esterase.

Erythroid

Erythroid differentiation in the leukemic population.

Megakaryocytic

Platelet-lineage antigens and possible marrow fibrosis.

Slide 46 · Morphologic common denominator

Every AML subtype increases immature myeloid cells in marrow.

Blasts vary morphologically and can have hybrid features.

The distribution between marrow and peripheral blood is variable.

Morphology is the starting point, not the whole diagnosis.

Slide 47 · Blast percentage and genetic exceptions

Marrow examination

Estimate proportions of immature myeloid cells

Conventional benchmark

Approximately 20% blasts in most AML

Defining genetic lesions

Some genetically defined entities use exceptions

Exact thresholds are classification- and entity-dependent; The textbook summary should not replace formal diagnostic criteria.

Slide 48 · Recognizing a myeloblast

Schematic — not a clinical specimen

Features to recognize

Delicate nuclear chromatin.

Usually two to four nucleoli.

Relatively abundant cytoplasm.

Fine azurophilic granules may occur.

Slide 49 · Why Auer rods matter

Schematic — not a clinical specimen

Features to recognize

Needle-like azurophilic inclusions.

Support myeloid differentiation.

Particularly numerous in APL.

Absence does not exclude AML.

Slide 50 · Auer rods: A useful but incomplete clue

The inclusions represent distinctive needle-like azurophilic granules.

Many, but not all, AML cases contain detectable Auer rods.

Abundant clustered rods are strongly associated with APL.

Diagnosis still requires integrated lineage and genetic testing.

Slide 51 · Monoblast morphology

Schematic — not a clinical specimen

Features to recognize

Folded or lobulated nuclear outline.

No typical Auer rods.

Nonspecific esterase-positive.

Can coexist with promonocytes in blood.

Slide 52 · Myeloblast versus monoblast

Myeloblast

Delicate chromatin; Often visible nucleoli.

Possible fine MPO-positive granules.

Auer rods may be observed.

Monoblast

Folded or lobulated nuclear membranes.

Nonspecific esterase reactivity.

Auer rods generally absent.

Slide 53 · Marrow fibrosis in megakaryocytic AML

Megakaryoblastic differentiation can be accompanied by fibrosis.

Leukemic cells release factors with fibrogenic effects.

Fibrosis may complicate marrow aspiration and interpretation.

Lineage-specific antigen studies help establish the phenotype.

Slide 54 · Peripheral counts cannot rule out AML

Leukemic cells circulate

Some patients have striking numbers of blood blasts.

Peripheral morphology may immediately suggest acute leukemia.

Leukemic cells scarcely circulate

Blasts may be few or absent despite marrow disease.

Pancytopenia requires marrow assessment when leukemia is suspected.

Slide 55 · Aleukemic leukemia: A diagnostic trap

The blood smear may lack visible circulating blasts.

Anemia, neutropenia and thrombocytopenia can predominate.

A reassuring peripheral blast count does not exclude AML.

Bone marrow examination remains essential in suspicious pancytopenia.

Slide 56 · Why immunophenotyping is necessary

Blast morphology

Myeloblasts and lymphoblasts may overlap

Lineage testing

Myeloid-specific antigen expression

Integrated diagnosis

Morphology + immunophenotype + genetics

Assigning myeloid lineage may require flow cytometry and/or cytochemistry.

Slide 57 · Flow cytometry: An illustrative Robbins example

Marker

Illustrated expression

Interpretive role

CD34

Positive

Stem/progenitor-associated blast marker

CD33

Positive

Myeloid-associated lineage marker

CD15

Subset positive

A measure of partial myeloid maturation

CD64

Negative

Lack of mature monocytic-marker expression

Slide 58 · Cytochemistry contributes to lineage assignment

Myeloperoxidase positivity supports granulocytic differentiation.

Nonspecific esterase helps identify monocytic differentiation.

Minimally differentiated AML can be MPO-negative.

Flow-cytometric immunophenotyping is essential when morphology is equivocal.

Slide 59 · A source-consistent diagnostic workflow

CBC / smear

Assess cytopenias and morphology

Marrow

Characterize blast expansion and lineage

Flow / stains

Confirm myeloid phenotype

Genetics

Assign entity and risk category

This is a teaching schematic; Testing choices should follow a current diagnostic protocol.

Slide 60 · Clinical context predicts different genetics

Younger, de novo AML

Balanced rearrangements such as t(8;21), inv(16), t(15;17) are relatively characteristic.

A subset has favorable biology.

Older / prior hematologic disease

Overlap with mutations in clonal hematopoiesis and MDS.

Adverse molecular patterns become more common.

Slide 61 · Therapy-related AML: Dominant patterns

Prior chemotherapy or radiation exposure can precede AML.

Most DNA-damaging exposures correlate with chromosome 5/7 lesions.

TP53 dysfunction and complex karyotypes are frequent.

The genetic signature contributes to an adverse clinical phenotype.

Slide 62 · Topoisomerase II therapy: A notable exception

AML after topoisomerase II inhibition can follow another genetic route.

KMT2A translocations involving 11q23 are emphasized.

Monocytic differentiation may accompany KMT2A rearrangement.

Exposure history and genetics should be interpreted together.

Slide 63 · Typical presentation evolves over weeks to months

Marrow replacement

Anemia + neutropenia + thrombocytopenia

Clinical manifestations

Fatigue + fever/infection + bleeding

Urgent workup

Marrow and lineage-specific investigations

Do not wait for leukocytosis or a large circulating blast fraction.

Slide 64 · Symptoms reflect lost normal cell function

Anemia

Fatigue, decreased activity tolerance and pallor.

Neutropenia

Fever and susceptibility to infection.

Thrombocytopenia

Petechiae, ecchymoses and mucosal bleeding.

Blast-specific effect

Tissue infiltration and coagulopathy in some subtypes.

Slide 65 · Hemorrhage in AML

Thrombocytopenia reduces primary hemostatic capacity.

Mucosal, cutaneous and serosal hemorrhage may occur.

Bleeding can involve gingivae or urinary tract.

APL adds a consumptive coagulopathy to the platelet deficit.

Slide 66 · APL-related bleeding is mechanistically distinct

Promyelocyte products

Procoagulant and fibrinolytic mediators

Hemostatic imbalance

Consumption and dysregulated fibrinolysis

Clinical result

DIC and potentially severe hemorrhage

APL with suspected coagulopathy requires urgent clinical recognition.

Slide 67 · Infections are a consequence of neutropenia

Loss of functional neutrophils impairs antimicrobial defense.

Infection commonly affects oral cavity, skin, lung and urinary tract.

Gastrointestinal and renal/urinary infections are also described.

Opportunistic fungi and Gram-negative bacteria may be involved.

Slide 68 · Extramedullary manifestations

Gingival infiltration

Particularly relevant in monocytic differentiation.

Leukemia cutis

Skin involvement by leukemic cells.

Myeloid sarcoma

A localized soft-tissue tumor of myeloid blasts.

Central nervous system

Less frequent involvement than in acute lymphoblastic leukemia.

Slide 69 · Myeloid sarcoma: A tissue-based presentation

AML occasionally produces a localized soft-tissue mass.

This mass may be recognized as myeloid sarcoma.

A tissue lesion may occur before florid systemic AML is apparent.

Without systemic treatment, progression to marrow disease is expected.

Slide 70 · Acute myeloid versus acute lymphoblastic leukemia

Shared mechanisms

Both can replace marrow and cause cytopenias.

Both may present with fever, fatigue or bleeding.

Useful distinction

Immunophenotype establishes myeloid or lymphoid lineage.

CNS involvement is relatively less frequent in AML.

Slide 71 · AML versus MDS in marrow failure

AML

Accumulation of immature myeloid blasts.

Abrupt clinical presentation is common.

Many cases meet a high blast burden or defining genetic pattern.

MDS

Defective maturation with ineffective production.

Dysplastic elements predominate.

May evolve into AML over time.

Slide 72 · Why prognosis depends heavily on genotype

Some rearrangements identify highly treatment-responsive disease.

TP53 abnormalities and complex karyotypes predict resistance.

Age, prior MDS and therapy-related disease shift genotype distribution.

A single undifferentiated AML survival estimate conceals this heterogeneity.

Slide 73 · Molecular categories and broad prognosis

Example

Textbook direction

Rationale

PML::RARA APL

Very favorable

Sensitive to ATRA / arsenic

t(8;21) or inv(16)

Favorable

Better conventional-therapy response

KMT2A / MDS-related AML

Often poor

Adverse molecular context

TP53-abnormal AML

Poor

Resistant disease; complex karyotype

Slide 74 · APL is a paradigmatic molecular success

PML::RARA is a specific therapeutic vulnerability.

Retinoic acid and arsenic trioxide overcome the fusion-associated block.

Cure in more than 90% of patients with this subtype.

The immediate bleeding risk remains essential to clinical recognition.

Slide 75 · Adverse-risk AML: The TP53 example

P53 pathway impairment associates with genomic complexity.

Marked dysplasia and erythroid differentiation may coexist.

Standard therapies often perform poorly.

Some high-risk or relapsed cases are considered for stem-cell transplantation.

Slide 76 · Targeted AML therapeutics: Two examples

Mutant IDH1 / IDH2

Altered metabolism yields 2-hydroxyglutarate.

Mutant-IDH inhibitors may produce strong responses.

Activating FLT3

Growth-factor-like signaling promotes blast survival.

FLT3 kinase inhibitors target the activated signaling enzyme.

Slide 77 · Other therapeutic concepts discussed

Epigenetic-modifying agents are therapeutic options for some older adults.

BCL2 inhibition can produce responses in AML.

Responses in these settings may be transient.

Treatment decisions depend on molecular risk and patient condition.

Slide 78 · HSC transplantation: A selected strategy

Used in some high-risk and relapsed AML settings.

Patient factors, remission status and disease genetics influence eligibility.

The treatment goal differs from purely symptom-directed management.

A pathology lecture should distinguish risk assessment from prescribing.

Slide 79 · Illustrative case: Promyelocytes and bleeding

A patient presents with new mucosal bleeding and cytopenias. Marrow shows many abnormal promyelocytes with dense granules and bundled Auer rods.

Discuss

What molecular lesion should be prioritized?

Which life-threatening hemostatic complication is associated?

Slide 80 · Case interpretation: Suspect APL

Likely subtype

AML with PML::RARA associated with t(15;17).

Morphologic clue

Hypergranular promyelocytes and numerous Auer rods.

Immediate concern

Disseminated intravascular coagulation and hemorrhage.

Mechanistic therapy

Retinoic acid and arsenic act on the fusion-dependent block.

Slide 81 · Illustrative case: Pancytopenia without blasts

An older adult has progressive fatigue, fever and widespread petechiae. The blood film shows pancytopenia but no unequivocal circulating blasts.

Discuss

Does the absence of blood blasts exclude AML?

Which specimen is essential for the diagnostic evaluation?

Slide 82 · Case interpretation: Marrow remains decisive

Peripheral film

Blasts may be absent

Persistent suspicion

Marrow replacement can still be present

Bone marrow analysis

Morphology, immunophenotype, genetics

Aleukemic presentation is a recognized diagnostic pitfall.

Slide 83 · Illustrative case: Gingival and skin lesions

A patient with acute marrow failure has gingival thickening and skin nodules. Blasts have folded nuclear membranes and nonspecific esterase positivity.

Discuss

Which lineage differentiation is favored?

How does the normal behavior of that lineage help explain tissue infiltration?

Slide 84 · Case interpretation: Monocytic AML

Lineage clue

Monoblasts or promonocytes with folded nuclei.

Cytochemistry

Nonspecific esterase supports monocytic differentiation.

Clinical association

Gingival infiltration and leukemia cutis.

Mechanistic link

Monocytes normally extravasate into tissues.

Slide 85 · Integrated diagnostic synthesis

Recognize AML

Marrow failure and immature myeloid cells

Confirm lineage

Morphology, flow cytometry, cytochemistry

Assign subtype

Defining genetics and maturation pattern

Interpret risk

Genotype plus clinical background

Each layer contributes distinct information; None should be interpreted in isolation.

Slide 86 · Five points to retain

AML is differentiation-arrested myeloid neoplasia with marrow failure.

Transcription-factor, signaling, epigenetic and TP53 alterations cooperate.

Auer rods support myeloid lineage; Absence does not rule out AML.

Molecular classification determines major biologic and therapeutic distinctions.

APL is simultaneously a bleeding emergency and a highly targetable subtype.

Slide 87 · Primary teaching reference

Robbins, Cotran & Kumar: Pathologic Basis of Disease, 11th edition.

Chapter 13: Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus.

Acute myeloid leukemia, classification, morphology and adjacent genetics/clinical features; printed pages 562–564.

Source images from textbook figures were not reproduced; drawings are original editable schematics.