Bone marrow neoplastic

• 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

• 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

WHO revised 4th edition	WHO 5th edition	ICC classification
AML with myelodysplasia related changes (AML-MRC) Blasts > 20% and no prior therapy	N/A Only inv(3)/t(3;3) described under acute myeloid leukemia with MECOM rearrangement (3q26 abnormalities)	AML with other rare recurring translocations Blasts > 10% AML with myelodysplasia related changes eliminated

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

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

• Variable and possibly related to the patient's distinct AML FAB type
• Usually positive
  • CD14, CD11b
• Variable positivity
  • CD34, TdT and CD7
  • CD13, CD33 and CD36
  • CD38, HLA-DR and CD117 (KIT)
• Possible abnormal expression of CD56, CD72
• Other myeloid markers may be positive
• Reference: Cancer Genet Cytogenet 2010;203:187

• 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).

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 show a distinct phenotype characteristic of this entity
2. Case shows overexpression of the PRDM16 gene
3. Frequently associated with NPM1 mutation
4. Has an intermediate prognosis

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)