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Leukemia - Acute

Recurrent genetic abnormalities

AML with myelodysplastic related changes

Reviewer: Daniela Mihova, M.D. (see Reviewers page)
Revised: 19 February 2013, last major update September 2012
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.


● 20%+ blasts in peripheral blood or bone marrow AND (a) prior diagnosis of MDS or MDS/MPN; (b) cytogenetic abnormalities associated with MDS or (c) multilineage dysplasia in > 50% of the cells of at least 2 separate bone marrow lineages
● Excludes patients with (a) prior history of cytotoxic therapy or unrelated disease or (b) cytogenetic abnormalities associated with AML with recurrent genetic abnormalities
● Arises either as de novo AML, from existing myelodysplastic syndrome or from myelodysplastic / myeloproliferative neoplasm
● Includes what was previously called refractory anemia with excess blasts in transformation
● Previously called AML with multilineage dysplasia
● Recommended to include reason for diagnosis, blast count or presence of mutations (NPM1, CEBPA, FLT3)
● Examples: (a) AML-MRC (multilineage dysplasia); (b) AML-MRC (previous MDS or MDS/MPN history); (c) AML-MRC (MDS related cytogenetics and presence of FLT3 mutation)

Clinical features

● Usually presents with severe pancytopenia
● Both children and adults; represent 24-35% of all AML
Children: occurs in 3% with de novo AML, good response to treatment (Int J Hematol 2007;86:358)
Adults: median age 61 years; higher incidence in AML in older individuals

Prognostic features

● Poorer prognosis than classic AML, particularly if adverse cytogenetics (Eur J Haematol 2002;68:203), and history of MDS or MDS/MPN (Blood 2010;116:2742), but see Blood 2008;111:1855
● Low blast count less clinically aggressive

Micro description

● Dysplasia in 50%+ of cells of 2 or more lineages
● Often panmyelosis, usually dysplastic megakaryocytes
● Variably cellular marrow with 20%+ blasts
Dysgranulopoiesis: hypogranular neutrophils, hyposegmented (Pelger-Hut cells) and bizarrely segmented (as seen in peripheral blood)
Dyserythropoiesis: megaloblastosis, karyorrhexis, nuclear irregularity, fragmentation, multinucleation, ringed sideroblasts, cytoplasmic vacuoles and PAS+
Dysmegakaryopoiesis: micromegakaryocytes, normal or large megakaryocytes with non-lobulated or multiple nuclei

Micro images

Various images
Patients with prior MDS

Images contributed by Daniela Mihova, MD:

Positive stains

● CD34, CD117 and HLA-DR

Molecular description

● Trisomy 8, abnormalities of #5 or #7 are common
● Also t(3;5)(q25;q34-35) involving MLF1 and NPM (Hum Pathol 2003;34:809)
● Mutations in NPM1, CEBPA, FLT3-ITD, FLT3-D835, N-RAS and MLL-PTD (Blood 2009;113:1906)
● Complex karyotype including 3+ unrelated abnormalities, none of which is included in AML with recurrent genetic abnormalities

● Unbalanced abnormalities: -7/del(7q), -5/del(5q), i(17q)/t(17p), -13/del(13q), del(11q), del(12p)/t(12p), del(9q), idic(X)(q13) (eMedicine)

● Balanced abnormalities:
● t(11;16)(q23;p13.3) - therapy related myeloid neoplasms should be excluded before diagnosis of AML-MRC
● t(3;21)(q26.2;q22.1) - therapy related myeloid neoplasms should be excluded before diagnosis of AML-MRC
● t(1;3)(p36.3;q21.1)
● t(2;11)(p21;q23) - therapy related myeloid neoplasms should be excluded before diagnosis of AML-MRC
● t(5;12)(q33;p12)
● t(5;7)(q33;q11.2)
● t(5;17)(q33;p13)
● t(5;10)(q33;q21)
● t(3;5)(q25;q34) young patients; involving MLF1 and NPM (Hum Pathol 2003;34:809)

● Common in MDS but not sufficient for diagnosis of AML-MRC by themselves: +8, del(20q), and loss of Y (in older man)

Differential diagnosis

Acute erythroid leukemia
Acute megakaryoblastic leukemia
● AML with recurrent genetic abnormalities

End of Leukemia - Acute > Recurrent genetic abnormalities > AML with myelodysplastic related changes

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