Bone marrow neoplastic
Bone marrow - neoplastic myeloid
Recurrent genetic abnormalities
AML with inv(3)(q21.3;q26.2) or t(3;3)(q21.3;q26.2)


Topic Completed: 21 December 2020

Minor changes: 31 December 2020

Copyright: 2020, PathologyOutlines.com, Inc.

PubMed Search: inv3 q21;q26.2 OR t3;3 q21;q26.2

Oluwatobi
Kamran M. Mirza, M.D., Ph.D.
Page views in 2020: 217
Page views in 2021 to date: 35
Cite this page: Odetola O, Mirza KM. AML with inv(3)(q21.3;q26.2) or t(3;3)(q21.3;q26.2). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowneoplasticAMLinv3q21q26.html. Accessed January 23rd, 2021.
Definition / general
Essential features
  • Aggressive form of AML with very poor prognosis and poor response to conventional induction chemotherapy (Cancer Genet 2019;230:28)
  • Diagnosed by presence of the pathognomonic cytogenetic abnormality inv(3)(q21q26.2) or t(3;3)(q21;q26.2) [inv(3) / t(3;3)] (Blood 2016;127:2391)
  • End result is juxtaposition of the distal GATA2 enhancer with the MECOM (EVI1) proto-oncogene (Blood 2016;127:2391)
  • May present as de novo disease or evolve from preexisting myelodysplastic syndrome (Cancer Genet 2019;230:28)
Terminology
  • AML with inv(3)
  • Acute myeloid leukemia with GATA2, MECOM
  • AML with RPN1 / EVI1
  • 3q21q26 syndrome (Hematology 2015;20:435)
  • AML with RPN1-MECOM
ICD coding
Epidemiology
Sites
  • Bone marrow
  • Peripheral blood
Pathophysiology
Etiology
Clinical features
  • Presence of at least 20% blasts in peripheral blood or bone marrow
  • Often presents with anemia
  • Elevated white blood cell count (sometimes low)
  • Normal or elevated platelet count
  • Association with central diabetes insipidus (Hematology 2015;20:435)
  • Elevated LDH
Diagnosis
  • Requires enumeration of 20% blasts on peripheral blood smear or marrow aspirate differential count(s)
  • Flow cytometry or immunohistochemical stains may assist in blast phenotyping
  • Juxtaposition of GATA2 and MECOM, inv(3)(q21q26.2) or t(3;3)(q21;q26.2) [inv(3) / t(3;3)] can be detected by classic cytogenetics, FISH and other molecular / genetic studies including chromosome microarray, next generation sequencing, RT-PCR, etc.
Laboratory
  • CBC with anemia
  • Leukocytosis (sometimes leukopenia) with 20% blasts
  • Normal or elevated platelet count
  • Elevated LDH
  • Flow cytometry analysis reveals increased dim CD45 events (blasts)
Prognostic factors
Case reports
Treatment
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Alexa J. Siddon, M.D.
Hypercellular marrow with increased blasts

Hypercellular marrow with increased blasts

Cytology images

Contributed by Alexa J. Siddon, M.D.
Aspirate with hypolobated mega

Aspirate with hypolobated megakaryocyte

Aspirate with blasts

Aspirate with blasts

Peripheral smear description
Positive stains
Negative stains
Flow cytometry description
Molecular / cytogenetics description
  • inv(3)(q21q26.2) or t(3;3)(q21;q26.2) [inv(3) / t(3;3)]
  • Increased expression of EVI1 (MECOM)
  • Relative haploinsufficiency of GATA2
  • Associated monosomy 7, complex karyotype and 5q deletion
  • Gene mutations identified include those of NRAS, GATA2, SF3B1, FLT3-ITD, KIT D816, PTPN11, CBL, KRAS and BCR-ABL1 and CEBPA (Blood 2015;125:133, Int J Lab Hematol 2019;41:380)
Molecular / cytogenetics images

Images hosted on other servers:

Double inv(3)(q21q26) and monosomy 7

FISH with EVI1 breakapart probe

Sample pathology report
  • Right posterior iliac crest, core biopsy, aspirate smear, touch imprint and clot particle:
    • Acute myeloid leukemia with inv(3)(q21.3;q26.2); GATA2, MECOM (see comment)
    • Comment: The bone core biopsy demonstrates an increase in blasts and prominent dysmegakaryocytopoiesis. The presence of inv(3)(q21.3;q26.2) confirms above diagnosis.
Differential diagnosis
  • Other AML with recurrent cytogenetic abnormalities:
    • Presence of other subtype defining cytogenetic abnormalities different from inv(3) / t(3;3)
  • MDS with inv(3):
    • Blast count < 20%
Board review style question #1
Which of the following is true about AML with inv(3) / t(3;3)?

  1. CD41 positivity on immunophenotypic studies is a key part of the diagnostic criteria
  2. Deletion of chromosome 5q is the most frequently associated cytogenetic abnormality
  3. Expression of CD7 is not consistent with the entity
  4. Expression of MECOM (EVI1) is commonly upregulated
  5. GATA2 fusion with MECOM (EVI1) is the characteristic molecular feature
Board review style answer #1
D. Expression of MECOM (EVI1) is commonly upregulated

Comment Here

Reference: AML with inv(3)(q21.3;q26.2) or t(3;3)(q21.3;q26.2)
Board review style question #2
Which of the following is true about AML with inv(3) / t(3;3)?

  1. Anemia and thrombocytopenia are hallmark findings on the peripheral smear
  2. Bone marrow is often hypocellular with extensive fibrosis
  3. Erythroid dysplasia is uncommon unlike in other subtypes of AML
  4. Finding of pseudo-Pelger-Hüet neutrophils suggest an alternative diagnosis
  5. Increased megakaryocytic dysplasia is commonly observed on bone marrow aspiration / biopsy
Board review style answer #2
E. Increased megakaryocytic dysplasia is commonly observed on bone marrow aspiration / biopsy

Comment Here

Reference: AML with inv(3)(q21.3;q26.2) or t(3;3)(q21.3;q26.2)
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