Acute Myeloid Leukemias (AML)MLAB 1415: HematologyKeri Brophy-Martinez

Overview of AML Also known as

Acute myelocytic leukemia Acute myelogenous leukemia Acute nonlymphocytic leukemia

Stem cell disorder characterized by malignant neoplastic proliferation and accumulation of immature and nonfunctional hematopoietic cells in the BM Chemo/radiation Exposure to benzene History of MDS

Overview of AML All acute leukemias begin BEFORE clinical signs and

symptoms occur As the tumor volume expands, normal functional

marrow cells decrease Characterized by two major features

Ability to proliferate continuously Due to mutations affecting growth factors Transcription errors

Arrested development of normal cells Lacks apoptosis

Etiology• Classified by the cellular

appearance of the primary stem cell• Common myeloid

progenitor (CMP)• AML or ANLL

• Common lymphoid progenitor (CLP)• ALL

• Peak incidence in adults over 60

Clinical findings

• CLASSIC TRIAD• Anemia• Infection• Bleeding/easy bruising/petechiae

• Fever• Shortness of breath• Fatigue• Weight loss• Pallor

Lab Features: Peripheral blood WBC count:

variable at diagnosis ( 1-200 x 109/L)

>20% blasts present Auer rods: fused primary granules in myeloblasts RBCs

Decreased Hgb < 10g/dL Inclusions reflect rbc maturation defects

Howell-Jolly, Pappenheimer, basophilic stippling

nRBCs present Platelets

Decreased Hypogranular, giant forms Megakaryocyte fragments

Lab Features: MISC.

• BONE MARROW• Hypercellular• Decreased fat content• >20 nonerythroid blasts• Fibrosis

• MISC• Hyperuricemic• Increased LDH

Who Classification of acute leukemia

• AML with recurrent genetic abnormalities• AML with myelodysplasia- related changes• AML and MDS- therapy related• AML- not otherwise categorized

WHO Classification of Acute Myelocytic Leukemias

FAB Classification of Acute LeukemiaMorphology MPO SBB Specific esterase Nonspecific esterase PAS

M0 Acute myeloblastic leukemia: mimally differentiated

>30% blastsNo granules

Not present Not present Not present Not present Not present

M1 Acute myeloblastic leukemia with no maturation

>30% blastsFew granules+/- Auer rods

Present Present Can be Present Not present Not present

M2 Acute myeloblastic leukemia with maturation

>30% blasts Granules common+ Auer rods

Present Present Can be Present Not present Not present

M3 Acute promyelocytic leukemia

>30% blastsProminent granules++ Auer rods Faggot cells

Present Present Present Not present Not present

M4 Acute myelomonocytic leukemia

>30% blasts>20%monocytes+ Auer rods

Present Present Present Present Not present

M4 eo Acute myelomonocytic leukemiaWith eosinophilia

>30% blasts>20%monocytes>5% abn eos+ Auer rods

Present Present Present Present Not present

M5 Acute monoblastic leukemia with or withour maturation

>30% blasts>80% monocytes with/without differentiation

Can be Present Can be Present Can be Present Present Not present

M6 Acute erythroleukemia

>30% myeloblasts>50% megaloblasts+ Auer rods

Present:Myeloblasts

Present:Myeloblasts

Present:Myeloblasts

Not Present Present:Erythroblasts

M7 Acute megakaryocytic leukemia

>30% MegakaryoblastsCytoplasmic budding

Not present Not present Can be Present Not present/Present Not present

M1: AML without maturation

• Myeloblast with Auer rod

• High N:C ratio• Fine chromatin• Prominent nuclei

M2: Aml with maturation

All stages of neutrophil maturation>20% myeloblastsAuer rods common

M3: promyelocytic leukemia (faggot cell)

Faggot cells with bundles of Auer rodsGenetic translocation t(15;17)Hypergranulation

M4: Acute myelomonocytic leukemia (AMML)

Monoblasts and promonocytes seenSome neutrophil precursors seenVacuolization often seen

M5: Acute monoblastic leukemia

MonoblastsPromonocytes

M6: Acute erythroid leukemia

Striking poikHigh number of RBC precursors>20 Myeloblasts

M7: Acute Megakaryoblastic Leukemia

• Peripheral blood• May see micromegakaryoblasts• Megakaryocyte fragments• Cytopenias• Dysplastic segmented neutrophils and platelets

• Bone marrow• Often get “dry tap” • Fibrosis

Prognosis of all AMLs and therapy

• Death often occurs from infection and hemorrhage in weeks to months unless therapy is started

• Chemotherapy• Reduces tumor load

• Bone marrow transplants

References• McKenzie, Shirlyn B., and J. Lynne. Williams. "Chapter 21."

Introduction. Clinical Laboratory Hematology. Boston: Pearson, 2010. Print