AML in Down Syndrome

Epidemiology and Etiology:

· Acute megakaryoblastic leukemia (70% of AML in DS)

· 20-30% of patients with transient myeloproliferative disorder subsequently develop non-remitting AML 1-3y later

· < 5 y (most)

Common sites:

· Blood

· Bone marrow

· Spleen (almost all)

· Liver (almost all)

Gross features:

·

Histologic features:

· May be morphologically indistinguishable from transient abnormal myelopoiesis / transient myeloproliferative disorder

· Pre-leukemic phase:

· Features of refractory cytopenia of childhood (RCC)

· Note: there is no distinction between MDS and AML in DS AML – both are included

· PB:

· Blasts

· Erythroid precursors occasionally

· Erythrocytes with considerable anisopoikilocytosis, sometimes dacryocytes

· Platelets decreased

· Giant platelets maybe

· BM:

· Blasts with particular features:

· Round to slightly irregular nuclei

· Moderate amount basophilic cytoplasm

· Cytoplasmic blebs maybe

· Coarse granules resembling basophilic granules in some

· MPO negative generally

· Erythroid precursors:

· Megaloblastic changes

· Dysplastic forms

· Bi- or trinucleated cells and nuclear fragments

· Dysgranulopoiesis maybe

· Dysplastic megakaryocytes maybe

· Dense network of reticulin fibres may make adequate BM aspiration difficult or impossible

Immunophenotype:

Marker:	Sensitivity:	Specificity:
CD34	50%	TAM usually +
CD56	70%	TAM usually +
CD117
CD13
CD33
CD7
CD4 (dim)
CD41	70%	TAM usually +
CD42
TPO-R
IL-3R
CD36
CD61
CD71
HLA-DR	30%
MPO (neg)
CD15 (neg)
CD14 (neg)
Glycophorin A (neg)

Molecular features:

· Cytogenetics:

· Trisomy 21 (constitutional)

· Trisomy 8 (13-44%)

· Rarely monosomy 7

· GATA1 mutations

· Considered pathognomonic of TAM or DS AML

Other features:

· Young children: favourable prognosis compared to non-DS children with AML

· older children: poorer prognosis compared to non-DS children with AML

References:

· Swerdlow. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue. 4th ed. WHO Publications; 2008.