Case 1: Acute myelogenous leukemia with t(6;11)(q27;q23)

  • Contributed by Gregory L. Blakey, M.D., S. Terence Dunn, Ph.D., and William F. Kern, M.D.
    Department of Pathology, University of Oklahoma Health Sciences Center
  • Published on-line July 2003

History:

A 15-year-old girl presented with pharyngitis and tonsillitis. Laboratory evaluation revealed marked leukocytosis, and the patient was referred to our tertiary care center for further workup.

Laboratory Data:

CBC and Peripheral Smear:

White blood count = 268 K/mm3

Hemoglobin = 10.5 gm/dL

Platelet count = 17 K/mm3

Figure 1a

Figure 1b

The peripheral smear showing 97% medium-to-large blasts, some with cytoplasmic granules.

Flow Cytometry:

Flow cytometry performed on peripheral blood demonstrated:

Marker %
CD4 54
CD13 97
CD19 0
CD33 92
HLA-DR 52
CD45 100
CD34 68

Molecular Studies:

RNA was isolated from peripheral blood for analysis by a multiplex RT-PCR system for typing/subtyping of leukemia (HemaVision®, DNA Technology A/S, Aarhus C, Denmark).

Figure 2

1.5% agarose gel stained with ethidium bromide. The final PCR reaction yielded an approximately 300 bp band in lane 2 (See Discussion); L = 100 bp ladder; 900 bp band = internal positive β-globin control).

Diagnosis:

Acute myelogenous leukemia (AML) with t(6;11)(q27;q23)

Discussion:

The HemaVision® leukemia typing/subtyping system is a multiplex RT-PCR assay which identifies 28 chromosomal abnormalities (2). Two rounds of nested PCR reactions are carried out on reversed transcribed cDNAs. The first round identifies a subgroup of possible rearrangements. Whichever subgroup is identified dictates which second, "split-out" PCR round will be run. In this case, the final PCR reaction indicates t(6;11)(q27;q23), as per the key provided by the manufacturer. The corresponding genes are AF6(6q27) and MLL (11q23).

The MLL-AF6 fusion, like most 11q23 translocations, portends a poor prognosis (3). In the short term, however, this patient did well with chemotherapy (daunorubicin, cytarabine, and etoposide) followed by a peripheral stem cell transplant. MLL may be involved in hematopoietic system development (1).

A combination of histologic, immunophenotypic, and molecular analyses allows a specific diagnosis to be rendered in new cases of leukemia. In addition, multiplex RT-PCR can be used to monitor for minimal residual disease (4).

References:

  1. Ernst P, et al. The role of MLL in hematopoiesis and leukemia. Current Opinion in Hematology 2002, 9: 282-287.
  2. HemaVision® Manual. DNA Technology A/S. Denmark.
  3. Mitterbauer G, et al. Monitoring of minimal residual disease in patients with MLL-AF6-positive acute myeloid leukaemia by reverse transcriptase polymerase chain reaction. British Journal of Haematology 2000, 109: 622-628.
  4. Strehl S, et al. Multiplex reverse transcriptase-polymerase chain reaction screening in childhood acute myeloblastic leukemia. Blood 2001, 97(3): 805-808.