American Society of Hematology

Case Study: Flow Cytometry Pattern in APL

The following case study focuses on flow cytometry pattern in acute promyelocytic leukemia (APL). Test your knowledge by reading the question below and making the proper selection.

All of the following are true regarding the flow cytometry pattern in APL except (choose one):

  1. The leukemic cells are commonly CD34 and (HLA)-DR negative.
  2. The leukemic cells are commonly CD2 and CD13 positive.
  3. The leukemic cells commonly have absent/low expression of CD11a, CD18, CD66b.
  4. The leukemic cells commonly have CD33 negativity.
  5. The leukemic cells are occasionally CD56 positive in an NK-variant of the disease.

Answer

  1. The leukemic cells commonly have CD33 negativity.

Explanation

The immunophenotype of blast cells in acute promyelocytic leukemia (FAB M3) has been well characterized over the past 20 years.1 This immunophenotype has been reported to show 100 percent sensitivity and 99 percent specificity for predicting APL molecular rearrangement.2 These cells are typically classified as CD34 and (HLA)-DR negative, with absent or low expression of CD11a, CD18 and CD66b.1 The CD2 antigen is a transmembrane glycoprotein that functions as an adhesion molecule through binding to CD15, CD58, and CD59, and mediates T-cell activation through signal transduction.3 CD13 is an antigen present or expressed on the majority of peripheral blood monocytes and granulocytes and a common finding in all forms of acute myeloid leukemia.1 The CD33 antigen typically has high and homogeneous expression in APL blast cells, and has received increased interest in recent years with the development of Gemtuzumab ozogamicin (anti-CD33 antibody) as a target for therapy.4 The CD56 antigen has been found to be prominent in the NK variant of APL as well as associated with the PLZF/RARA fusion gene. Initial studies have shown that this gene is characterized by a predominance of blasts with regular nuclei and an increased number of Pelger-like cells, but its impact on survival is unclear.5,6

References

  1. Orfao A, Chillón MC, Bortoluci AM, et al. The flow cytometric pattern of CD34, CD15, and CD13 expression in acute myeloblastic leukemia is highly characteristic of the presence of PML-RARα gene rearrangements. Haematologica. 1999;84:405-12.
  2. Lin P, Hao S, Medeiros LJ, et al. Expression of CD2 in acute promyelocytic leukemia correlates with short form of PML-RARα transcripts and poorer prognosis. Am J Clin Pathol. 2004;121:402-7.
  3. Douer D, Preston-Martin S, Chang E, et al. High frequency of acute promyelocytic leukemia among Latinos with acute myeloid leukemia. Blood. 1996;87:308-13.
  4. Lo-Coco F, Cimino G, Breccia M, et al. Gemtuzumab ozogamicin (Mylotarg) as a single agent for molecularly relapsed acute promyelocytic leukemia. Blood. 2004;104(7):1995-9.
  5. Ferrara F, Morabito F, Martino B, et al. CD56 expression is an indicator of poor clinical outcome in patients with acute promyelocytic leukemia treated with simultaneous all-trans-retinoic acid and chemotherapy. J Clin Oncol. 2000;18:1295-300.
  6. Sainty D, Liso V, Cantù-Rajnoldi A, et al. A new morphologic classification system for acute promyelocytic leukemia distinguishes cases with underlying PLZF/RARA gene rearrangements. Blood. 2000;96:1287-96.

Case study submitted by Tim Wassenaar, MD, of the University of Wisconsin Hospital and Clinics.

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