Bone marrow neoplastic

Bone marrow - neoplastic myeloid

AML with other rare recurrent translocations

AML (megakaryoblastic) with t(1;22)(p13.3;q13.1); RBM15::MRTF1

Editorial Board Member: Patricia Tsang, M.D., M.B.A.
Deputy Editor-in-Chief: Genevieve M. Crane, M.D., Ph.D.
Hans Magne Hamnvåg, M.D.
Kamran M. Mirza, M.D., Ph.D.

Last author update: 1 April 2021
Last staff update: 27 April 2023

Copyright: 2020-2024,, Inc.

PubMed Search: AML t1;22

Hans Magne Hamnvåg, M.D.
Kamran M. Mirza, M.D., Ph.D.
Page views in 2023: 944
Page views in 2024 to date: 155
Cite this page: Hamnvåg HM, Mirza KM. AML (megakaryoblastic) with t(1;22)(p13.3;q13.1); RBM15::MRTF1. website. Accessed February 23rd, 2024.
Definition / general
Essential features
  • Rare subtype of AML with recurrent genetic abnormalities and differentiation along the megakaryocytic lineage
  • Defined by t(1:22)(p13.3;q13.1); RBM15-MKL1
  • Blasts are positive for platelet specific markers CD41a+, CD42b+, CD61+
  • Occurs most commonly de novo in infants and young children (aged ≤ 3 years) without Down syndrome
  • Severe disease often with poor prognosis
  • Acute myeloid leukemia (megakaryoblastic) with t(1;22)(p13.3;q13.1); RBM15-MKL1
  • AMKL with t(1:22)(p13.3;q13.1); RBM15-MKL1
  • RBM15 and MKL1 are also referred to as OTT and MAL, respectively
  • Abbreviations RBM15, MKL1, OTT and MAL stand for RNA binding motif protein 15, megakaryoblastic leukemia 1, OneTwoTwo and megakaryoblastic acute leukemia
ICD coding
  • ICD-O: 9911/3 - Acute myeloid leukemia (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1
  • Bone marrow, spleen and liver
  • Lymph node involvement can also occur
  • Postulated normal counterpart: myeloid progenitor cell with predominant megakaryocytic differentiation
  • RBM15-MKL1 fusion gene arising from the t(1;22)(p13.3;q13.1) is thought to be the initiating event (Blood 2015;126:943, Nat Genet 2001;28:220)
  • RBM15 encodes a protein with RNA recognizing motifs and a split end paralogue and orthologue C terminal (SPOC) domain that interact with the SMRT and NCoR corepressor complexes and the transcription factor downstream of Notch signaling named RBPJ (EMBO J 2002;21:5417, Genes Dev 2003;17:1909)
  • Product of MKL1 acts as a transcriptional coactivator of serum response factor (SRP), a transcription factor that regulates genes involved in cell growth, proliferation, differentiation and genes controlling the actin cytoskeleton (Blood 2010;116:1942)
  • Fusion of RBM15 and MKL1 may influence chromatin organization, differentiation induced by the HOX pathway and extracellular signaling pathways (Proc Natl Acad Sci USA 2001;98:5776)
Clinical features
  • Bone marrow biopsy
  • Cytogenetics
  • Molecular genetics
  • Immunophenotyping
  • Karyotype analysis showing evidence of t(1;22)(p13.3:q13.1) or molecular genetic evidence demonstrating RBM15-MKL1 fusion
Prognostic factors
Case reports
  • Chemotherapy (combination of an anthracycline and cytarabine)
Microscopic (histologic) description
  • Mixture of small and large megakaryoblasts may be found in the bone marrow and peripheral blood together with more undifferentiated blast cells with high N:C ratio
  • Megakaryoblasts are most often medium sized to large (12 - 18 μm)
    • Nucleus is round, slightly irregular / indented with fine reticular chromatin and 1 - 3 nucleoli
    • Cytoplasm is basophilic, often agranular, with distinct blebs or pseudopod formation
  • Bone marrow is normocellular to hypercellular, with varying degrees of reticulin and fibrosis
  • Establishing the presence of ≥ 20% blasts on bone marrow aspirate may prove difficult due to extensive fibrosis; making correlation with bone marrow biopsy findings crucial
  • Micromegakaryocytes are commonly present
  • Dysplastic erythroid and granulocytic cells are usually not seen
Positive stains
  • Platelet glycoproteins:
    • CD41 (glycoprotein IIb / IIIa)
    • CD61 (glycoprotein IIIa)
    • CD42b (glycoprotein Ib)
  • Myeloid markers may also be positive
  • CD36
Negative stains
Flow cytometry description
  • Blasts are CD41a+, CD42b+, CD61+
Molecular / cytogenetics description
  • Translocation t(1;22)(p13.3;q13.1) is visible on karyotype (Nat Genet 2001;28:220)
  • Detection of RBM15-MRTFA (MKL1) fusion transcript via RT-PCR
Sample pathology report
  • Right posterior iliac crest, core biopsy, aspirate smear, touch imprint and clot particle:
    • Acute myeloid leukemia (megakaryoblastic) with t(1;22)(p13.3;q13.1); RBM15-MKL1 (see comment)
    • Comment: The bone core biopsy demonstrates extensive replacement of marrow by blast cells in areas arranged into clusters and aggregates surrounded by fibrotic stroma. The marrow aspirate smears reveal a heteromorphic population of blasts. Blast phenoptyping with immunohistochemical stains and flow cytometry analysis reveal positivity for markers of megakaryocytic maturation. Cytogenetics evaluation reveals t(1;22)(p13.3;q13.1), confirming above diagnosis.
Differential diagnosis
Board review style question #1
What is the resulting fusion gene product in t(1;22)(p13.3;q13.1) that is recurrent in one of the acute leukemic entities?

  1. DEK-NUP214
  2. KMT2A-MLLT3
  4. RBM15-MKL1
  5. RUNX1-RUNX1T1
Board review style answer #1
Board review style question #2
Which of the following populations have the highest incidence of acute megakaryoblastic leukemia (AMKL) with t(1;22)(p13.3;q13.1)?

  1. Children aged 5 - 10
  2. Elderly females
  3. Elderly males
  4. Infants with Down syndrome
  5. Infants without Down syndrome
Board review style answer #2
E. Infants without Down syndrome

Comment Here

Reference: AML (megakaryoblastic) with t(1;22)(p13.3;q13.1)
Board review style question #3
Which of the following markers is mostly likely to be negative in AMKL with t(1;22)(p13.3;q13.1)?

  1. CD13
  2. CD36
  3. CD41
  4. CD61
  5. Myeloperoxidase
Board review style answer #3
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