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AML with other rare recurrent translocations

AML with t(1;3)(p36;q21); RDM16::RPN1


Maxwell Walters-Smith, B.S., B.A.
Hatem Kaseb, M.D., Ph.D., M.P.H.

Last staff update: 21 September 2023 (update in progress)

Copyright: 2022-2023, PathologyOutlines.com, Inc.

PubMed Search: AML with t(1;3)(p36;q21)

Maxwell Walters-Smith, B.S., B.A.
Hatem Kaseb, M.D., Ph.D., M.P.H.
Page views in 2023 to date: 163
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Peripheral smear images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2
Cite this page: Walters-Smith M, Kaseb H. AML with t(1;3)(p36;q21); RDM16::RPN1. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowneoplasticAMLt13p36q21.html. Accessed September 27th, 2023.
Definition / general
  • Rare type of acute myeloid leukemia (AML)
  • AML with myelodysplastic syndrome (MDS) related changes (WHO, 2017)
    • Balanced translocation meeting criteria for AML with MDS related changes
    • Blasts > 20% and no prior therapy
  • Described as an entity under the category of AML with other rare recurring translocations in International Consensus Classification (ICC) (Blood 2022;140:1200)
  • AML with fusion of PRDM16 and RPN1
Essential features
Terminology
  • Acute myeloid leukemia with t(1;3)(p36;q21) (PRDM16::RPN1)
  • AML with t(1;3)(p36;q21) (PRDM16::RPN1)
ICD coding
  • ICD-O: 9895/3 - acute myeloid leukemia with myelodysplasia related changes
Epidemiology
Sites
  • Bone marrow, spleen and liver
  • Lymph node involvement can also occur
Pathophysiology
  • Genes at break point of translocation include RPN1 at 3q21.3 and group of genes at PRDM16 at 1p36.3 (Br J Haematol 2012;156:76)
  • Related to chromosome 3 abnormalities, such as inv(3)(q21q26), t(3;3)(q21;q26), ins(3;3)(q26;q21q26) and t(1;3)
    • t(1;3) show dysmegakaryopoietic features similar to the 3q21q26 syndrome
  • PRDM16 gene (MEL1, MDS1::EVI1-like gene) is activated as a result of translocation of the gene next to RPN1 gene at 3q21 (Genes Chromosomes Cancer 2003;36:313)
    • PRDM16 gene at 1p36.3 (the breakpoints are located within a 90 kb region in the 5' region of PRDM16)
    • RPN1 gene at 3q21 (the breakpoints are located within a 60 kb region centromeric to the breakpoint cluster region of the 3q21q26 / inv(3) syndrome)
    • Aberrant expression of PRDM16 as a result of RPN1 translocation is thought to be associated with pathogenesis of this AML subtype
Etiology
  • Aberrant expression of PRDM16 as a result of RPN1 translocation
Clinical features
  • Majority of cases present
    • Anemia (common)
    • Thrombocytosis and leukocytosis
    • Pancytopenia
  • Some cases present as MDS and then progress to AML (WHO, 2017)
  • Translocation (1;3) can be the sole chromosomal abnormality at initial diagnosis or can be associated with other chromosomal abnormalities
  • Peripheral thrombocytosis is a distinct feature (Cancer Genet Cytogenet 2010;203:187)
  • t(1;3) was first reported in 1984 (Blood 1984;64:553)
  • Aberrant expression of PRDM16 as a result of RPN1 translocation is associated with various other hematological conditions (Cancer Genet Cytogenet 2010;203:187)
    • MDS
    • Myelodysplastic / myeloproliferative neoplasms (MDS / MPN)
    • Myeloproliferative neoplasms (MPN)
    • AML
    • Acute lymphoblastic leukemia (ALL)
  • Prognosis is poor; median survival is ~6 months
  • WHO diagnostic criteria (WHO, 2017)
    • > 20% peripheral blood or bone marrow blasts
    • Any of the following:
      • History of MDS or MDS / MPN
      • MDS related cytogenetic abnormality
      • Multilineage dysplasia
    • Absence of both of the following:
      • Prior cytotoxic or radiation therapy
      • Recurrent cytogenetic abnormalities of AML
Diagnosis
  • Peripheral blood
  • Bone marrow biopsy
  • Cytogenetics
    • Karyotype analysis showing (1;3)(p36;q21) (PRDM16::RPN1)
  • Molecular genetics
  • Immunophenotyping
Laboratory
Prognostic factors
Case reports
Treatment
  • No specific treatments for this specific translocation have been reported
  • Chemotherapy
  • Stem cell transplantation
Microscopic (histologic) description
  • Presentation as AML (M1 - M5) has been reported; however, presentation as AML M4 (French American British [FAB] classification) is common (Cancer Genet Cytogenet 2010;203:187)
  • Prominent monocytic component has been reported in some cases
  • Multilineage dysplasia especially dysmegakaryopoiesis (Cancer Genet Cytogenet 2010;203:187, Genes Chromosomes Cancer 2003;36:313)
    • At least 50% dysplasia across 2 different lineages (WHO, 2017)
  • Megakaryocytes
    • Megakaryocytic hyperplasia and dysplasia
  • Peripheral thrombocytosis is a distinct feature
Microscopic (histologic) images

Contributed by Hatem Kaseb, M.D., Ph.D., M.P.H.
Numerous blasts

Numerous blasts

Numerous blasts and myelodysplasia related changes

Numerous blasts and myelodysplasia related changes

Peripheral smear images

Contributed by Hatem Kaseb, M.D., Ph.D., M.P.H.
Scattered blasts

Scattered blasts

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Right posterior iliac crest, core biopsy, aspirate smear, touch imprint and clot particle:
    • Acute myeloid leukemia with t(1;3)(p36;q21) (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 an increased population of blasts. Blast phenotyping with immunohistochemical stains and flow cytometry analysis reveal positivity for myeloid markers. Cytogenetics evaluation reveals t(1;3)(p36;q21). Overall, the results support the diagnosis of AML with t(1;3)(p36;q21).
Differential diagnosis
Board review style question #1


A 60 year old woman presented with fatigue and weight loss. The patient's initial laboratory workup showed leukocytosis, anemia and thrombocytosis. A bone marrow biopsy was performed, which showed increased blasts and multilineage dysplasia. A karyotype showed with t(1;3)(p36;q21). Which of the following is true about this entity?

  1. Blasts are frequently CD34 positive
  2. Case shows overexpression of the PRDM16 gene
  3. Frequently associated with NPM1 mutation
  4. Has an intermediate prognosis
Board review style answer #1
B. Case shows overexpression of the PRDM16 gene. Overexpression of the PRDM16 gene as a result of RPN1 translocation is an important finding in in AML t(1;3)(p36;q21) patients. Answer A is incorrect because flow cytometry is usually nonspecific in AML t(1;3)(p36;q21). Answer C is incorrect because NPM1 mutation has not shown to be associated with AML t(1;3)(p36;q21). Answer D is incorrect because these cases typically show a poor prognosis.

Comment Here

Reference: AML with t(1;3)(p36;q21)
Board review style question #2
A 53 year old man presented with thrombocytopenia and leukocytosis and is found to have t(1;3)(p36;q21) present in blast cells, with myeloblast cells composing 30% of cells in peripheral blood. Patient history includes prior AML diagnosis without t(1;3)(p36;q21), for which he was treated with chemotherapy, including an alkylating agent and achieved complete remission. What is the best current diagnosis?

  1. Acute myeloid leukemia, NOS
  2. Acute myeloid leukemia with myelodysplasia related changes
  3. Myelodysplastic syndrome with excess blasts
  4. Therapy related malignant neoplasm (AML)
Board review style answer #2
D. Therapy related malignant neoplasm (AML). This patient has a history of MDS and cytotoxic therapy and should therefore be diagnosed with therapy related malignant neoplasm (AML). Answer B is incorrect because patients with a history of MDS, no history for cytotoxic therapy and t(1;3)(p36;q21) should be diagnosed as acute myeloid leukemia with myelodysplasia related changes. Answer A is incorrect because AML, NOS is a diagnosis of exclusion when all other translocations and types have been thoroughly excluded. Answer C is incorrect because myelodysplastic syndrome with excess blasts should be considered in patients presenting with blasts < 20% in peripheral blood or bone marrow.

Comment Here

Reference: AML with t(1;3)(p36;q21)
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