Acute Myeloid Leukemia with t(8;21)(q22;q22), RUNX1-RUNX1T1

Acute Myeloid Leukemia with t(8;21)(q22;q22), RUNX1-RUNX1T1

Kaaren K. Reichard, MD

Peripheral blood smear shows 3 circulating blasts, 1 with a classic, thin Auer rod with tapered ends image in acute myeloid leukemia with translocation t(8;21)(q22;q22).

Karyogram reveals the recurring abnormality translocation (8;21)(q22;q22) in a case of de novo AML. Note the abnormal chromosomes image.



  • Acute myeloid leukemia (AML)

  • AML with t(8;21)(q22;q22), RUNX1-RUNX1T1


  • AML with maturation

  • AML M2 in French-American-British classification

  • Core binding factor AML

  • AML with AML1-ETO fusion


  • AML with specific genetic finding

    • t(8;21)(q22;q22) or variant or RUNX1-RUNX1T1 (a.k.a. AML1-ETO) gene fusion

  • Blast count may not meet typical requirement of ≥ 20%

    • So-called low blast count AML or oligoblastic AML

    • AML is defined by presence of genetic abnormality, regardless of blast count


Environmental Exposure

  • None identified for de novo AML with t(8;21)

  • Therapy-related AML with t(8;21)

    • Prior exposure to cytotoxic agents &/or radiotherapy

Molecular Pathogenesis

  • Normal

    • Core binding factor (CBF) alpha subunit (a.k.a. RUNX1) interacts with CBF beta subunit

    • CBF alpha and beta form transcription factor complex

    • CBF alpha subunit binds to DNA promoter sequences involved in hematopoiesis

  • Abnormal

    • t(8;21) results in chimeric fusion protein RUNX1-RUNX1T1

    • Downregulates normal transcriptional activity

  • “Multi-hit” model of AML

    • Class 1 and class 2 mutations

    • RUNX1-RUNX1T1 fusion is considered a class 2 mutation

      • Insufficient alone for leukemia formation

    • Development of overt leukemia requires concurrent class 1 mutation (e.g., KIT, FLT3, or RAS mutation)

Discovery of t(8;21)

  • 1st AML reciprocal translocation identified with common banding techniques (1975)

Association with Systemic Mastocytosis

  • AML with t(8;21) is most common AML associated with mastocytosis

  • WHO 2008 terminology

    • Systemic mastocytosis with associated hematological non-mast cell lineage disease (SM-AHNMD)

  • KIT D816V mutation in blasts and mast cells may indicate common progenitor



  • Incidence

    • 10-15% of pediatric AML cases

    • 7% of adult AML cases

  • Age

    • Predominates in younger patients (20-40 years)

  • Gender

    • Equal male:female ratio

  • Ethnicity

    • More frequent in African-Americans than Caucasians compared to AML with inv(16)


  • Abnormal CBC

    • Anemia

    • Thrombocytopenia

    • Single, bi-, or pancytopenia

    • Variable white blood cell count

    • Variable percent blast count

    • Neutropenia common

  • Myeloid neoplasm

    • Myeloid sarcomas common

      • Skin and gingival involvement


  • Chemotherapy

    • Cytarabine-based regimen


  • Favorable risk

  • Complete remission common

    • Especially with intensive postremission treatment

      • Multiple cycles of high-dose cytarabine

    • 50-60% cured with contemporary treatment

  • Prognostic genetic factors

    • ˜ 70% of patients harbor an additional chromosomal abnormality

      • -Y; worse overall survival

      • -X; no obvious impact

      • del(9q); better overall survival in non-white individuals

      • +8; no impact

    • KIT mutations

      • Found in 12-47% of patients

      • Occur mostly in exon 17

      • May confer adverse prognosis

    • FLT3 mutations

      • Infrequent; 4-12%

      • Internal tandem duplication and point mutations in the tyrosine kinase domain

      • Prognostic significance unknown

      • Some reports suggest worse prognosis

  • Minimal residual disease monitoring

    • Quantitative RT-PCR studies

      • Goal: Identify molecular remission while on therapy

      • Molecular remission predictive of durable complete remission

      • Absence of RUNX1-RUNX1T1 fusion may not be necessary for long-term remission

      • > 1 log increase in transcript levels associated with increased relapse risk


Extramedullary Involvement

  • Less common than in AML with inv16

  • Gingival hyperplasia

  • Splenomegaly rare

  • Cutaneous involvement


Key Microscopic Features

  • Peripheral blood

    • Anemia

    • Thrombocytopenia

    • Circulating blasts; possibly with Auer rods

    • Generally leukocytosis dominated by blasts

    • Evidence of neutrophilic maturation

    • Occasionally monocytic component

    • WBC count rarely exceeds 100 × 109/L

  • Bone marrow aspirate

    • Increased myeloid blasts

    • Variable blast count

      • Some cases less than the required 20% (low blast count AML)

    • Characteristic Auer rods

      • Thin with tapered, “cigar-shaped” ends

      • Usually single within a cell

      • Seen in cytoplasm of blasts and maturing/mature granulocytes

    • Abnormal neutrophilic precursors

      • Numerous pink/salmon-colored granules

      • Granules may abnormally aggregate in discrete region of cytoplasm

      • Dysplastic nuclei with megaloblastoid change and abnormal nuclear segmentation

    • In < 20% of cases, monocytic component

    • Erythroid and megakaryocytic lineages often decreased due to marrow replacement by AML

    • Increased and atypical, spindled mast cells if concurrent systemic mastocytosis

  • Bone marrow core biopsy

    • 100% cellular

    • With an increasing proportion of neutrophilic maturation, sheets of blasts may not be conspicuous

    • Megakaryocytic lineage is decreased but morphologically unremarkable

    • May see associated mast cell disease

      • Focal, compact, dense aggregates of mast cells

      • Mast cell aggregates may be overshadowed by the AML (so-called occult mastocytosis)

      • Mastocytosis is often revealed after treatment of AML

      • Osteosclerotic bone



  • Myeloperoxidase: Myeloblasts positive


  • Increased blasts: CD34, CD117 positive

    • May show Pax-5 positivity

  • Associated mast cell disease: Mast cells positive for tryptase &/or CD117, CD25 &/or CD2

Flow Cytometry

  • Myeloblasts: CD34, CD33, CD13, weak CD45

  • Aberrant antigen expression common

    • B-associated antigens: CD79a, CD19

    • TdT

    • CD56

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Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Acute Myeloid Leukemia with t(8;21)(q22;q22), RUNX1-RUNX1T1
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