Leukemia - Acute
Recurrent genetic abnormalities
AML with myelodysplastic related changes

Author: Daniela Mihova, M.D. (see Authors page)

Revised: 30 March 2018, last major update February 2013

Copyright: (c) 2001-2018, PathologyOutlines.com, Inc.

PubMed Search: AML with myelodysplastic related changes

Cite this page: Mihova, D. AML with myelodysplastic related changes. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/leukemiaAMLmulti.html. Accessed July 21st, 2018.
Definition / general
  • 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 AM
  • 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 factors
Microscopic (histologic) description
  • Dysplasia in 50%+ of cells of 2 or more lineages
  • Often panmyelosis, usually dysplastic megakaryocyte
  • Variably cellular marrow with 20%+ blasts
  • Dysgranulopoiesis: hypogranular neutrophils, hyposegmented (Pelger-Huët 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 nonlobulated or multiple nuclei
Microscopic (histologic) images

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Images contributed by Daniela Mihova, MD:


Positive stains
Molecular / cytogenetics 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: Pathology of Acute Myeloid Leukemia With Myelodysplasia-Related Changes [Accessed 30 March 2018])

  • 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