ACUTE MYELOID

LEUKEMIA
DONE BY ROLL NO.31 -45
 CONTENTS
1. Introduction
2. Pathogenesis
3. Morphology
4. Classification
5. Immunophenotype
6. Clinical features
7. Prognosis
8. Treatment
 AML
It’s a neoplasm of hematopoetic progenitors characterized by proliferation
resulting in accumulation of immature myeloblasts in bone marrow.
AML primarily affects older adults;median age is 50 years.
Clinical signs and symptoms closely resemble those produced by ALL.
AML mimics a lymphoma by manifesting as a discrete tissue mass(granulocystic
sarcoma)
 PATHOGENESIS
Most AML harbor mutations in genes encoding transcription factors that
are required for normal myeloid cell differentiation.
In promyelocytic leukemia (15;17) translocation

fusion of RARA(retinoic acid receptor alpha) on ch 17 + PML gene on ch15

PML/RARA fusion protein

Inhibit the function of normal retinoic acid receptors

Blocks myeloid differentiation at promyelocyte stage

 MORPHOLOGY
In AML myeloid blasts or promyelocytes makeup more than 20% of bone marrow cellularity.
Myeloblasts have delicate nuclear chromatin ,3-5 nucleoli and fine azurophillic granules.
Auer rods distinctive red staining ,rod like structures,may be present in myeloblast or more
differentiated cell.these are specific for neoplastic myeloblast and thus are a helpful diagnostic
clue when present.
In other subtypes of AML-monoblasts,erythroblasts or megakaryoblasts predominate.
Auer rods
 CLASSIFICATION
1. AML WITH RECURRENT CHROMOSMAL TRANSLOCATIONS

AML with t(8;21)(q22;q22);RUNXTI/ RUNXI fusion gene

AML with inv(16)(p13;q22)CBFB/MYHII fusion gene
AML with t(15;17)(q22;q21.1);PML/RARA fusion gene
AML with t(11q23;variant);MLL fusion gene
AML with mutated NPMI
2. AML WITH MULTILINEAGE DYSPLASIA
With previous MDS
Without previous MDS

3. AML THERAPY RELATED

Alkylating agent-related
Epipodophyllotoxin-related

4. AML NOT OTHERWISE CLASSIFIED

4. AML NOT OTHERWISE CLASSIFIED
AML minimally differentiated(M1)
AML without maturation(M2)
AML with maturation(M3)
Acute Myelomonocytic Leukemia(M4)
Acute Monoblastic and Monocytic Leukemia(M5)
Acute Erythroid Leukemia(M6)
Acute Megakaryoblastic Leukemia(M7)
IMMUNOPHENOTYPE
Expression of immunologic markers are heterogenous in AML.most tumors express some
combination of myeloid associated antigens such as CD13,CD14,CD15,CD64 orCD117(KIT)
CD34 is a marker of hematopoetic stem cells is often present on myeloblasts.
Such markers are helpful in distinguishing AML from ALL.
CLINICAL FEATURES
Most patients present within a week or few months of onset of symptoms with complaints
related to
Anemia-fatigue
Neutropenia-fever
Thrombocytopenia-spontaneous mucosal and cutaneous bleeding
Cutaneous petechiae and ecchymoses,serosal hemorrhages into linings of body cavity and
viscera and mucosal hemorrhages into the gingivae and urinary tract are common.
Oppourtunistic infections are frequent.
Gingival hyperplasia and ulceration and bleeding of
gingiva
PROGNOSIS
AML remains a devastating disease.
Tumors with good risk karyotyping abnormalities(t[8;21],inv[16])are associated with 50% chance
of long term disease free survival but the overall survival in all patients is only 15-30% with
conventional chemotherapy.
AMLs associated with tp53 mutations have poor prognosis.
TREATMENT
In treatment of acute promyelocytic leukemia targeted treatment with ATRA(all trans retinoic
acid-analogue of vitamin A) and arsenic salts have brought better outcomes.
IDH inhibitors have also produced encouraging results by inducing differentiation of AML blasts.
An increasing number of patients with AML are being treated with more aggressive approaches
such as allogenic hematopoetic stem cell transplantation which can be curative in some
patients.
REFERENCE
Robbins basic pathology
Google images
THANK YOU