BMW54: ACUTE MYELOID LEUKEMIA, NOT OTHERWISE SPECIFIED, WITH MLL
AMPLIFICATION
Kristian T Schafernak1, Katrin Carlson Leuer2 and LoAnn C Peterson3
1.Elmhurst Memorial Hospital, Pathology and Laboratory Medicine, Elmhurst, Illinois, USA
2.Children's Memorial Hospital, Pathology and Laboratory Medicine, Chicago, Illinois, USA
3.Northwestern Memorial Hospital, Pathology, Chicago, Illinois, USA
kristianschafernak@hotmail.com
Clinical history: The patient, a 55 yo woman, presented with a two week history of easy bruising,
spontaneous epistaxis and headache. She experienced gingival bleeding while brushing her teeth one day
before visiting her primary care physician, who noted a WBC count of ~30K/uL with immature cells. She was
referred to our institution for further evaluation and management.
Hb 8.9 g/dL, WBC 28.1K/uL, Plt 50K/uL.
Microscopy: Biopsy: Variably hypercellular bone marrow, overall 80-90%, largely replaced by blasts. Smear:
The peripheral blood smear shows neutrophilia with shift to immaturity including circulating blasts. Many of the
neutrophils are dysplastic, with prominent granulation and some cells featuring hypo- or abnormal nuclear
segmentation. The majority of abnormal neutrophils are negative for myeloperoxidase (MPO) by
cytochemistry. The bone marrow aspirate consists primarily of intermediate-sized to large blasts, some with
lobulated or indented nuclei. Auer rods are not seen. Rare blasts are MPO positive but, as in the peripheral
blood, the majority of abnormal neutrophils are MPO negative. Occasional cells show non-specific esterase
activity.
Immunophenotype/immunohistochemistry: Flow cytometry: Based on CD45 staining versus side scattered
light intensity characteristics, the red blood cell lysis prepared bone marrow aspirate contained 97% immature
cells with the following immunophenotype: dim CD34+*, CD117+, CD13+,** CD33+, dim MPO+, dim CD15+**,
dim CD11b+, dim CD64+, and dim CD14+; negative for lymphoid-associated antigens. (*heterogeneous
dim/negative to bright; **heterogeneous dim/negative to moderately bright positive, partial).
Immunohistochemistry: MPO on the biopsy showed that most of the blasts appear negative. Scattered
maturing and mature neutrophils are positive.
Cytogenetics: FISH for PML/RARa and MLL-DC: nuc ish amp(MLL)/nuc ish(MLLx2), nuc
ish(PMLx3),(RARax2)/nuc ish(PMLx2)(RARax2)
Abnormal mosaic female karyotype: clone 1 50~53,XX,+6,r(11)(?),+r(11)(?),+der(11)(?)x3,
+15,add(21)(p11.2),+22[cp17]; clone 2 53~54,idem,+8,+13[cp3]
Comment: G-band analysis initially identified 1-3 small fragments and 1-2 ring chromosomes in each cell.
FISH analysis with a probe to MLL showed that both the fragment and the rings were derived from
chromosome 11. The fragments contained approximately 1 copy of MLL and the rings contained multiple
copies of MLL resulting in amplification of the MLL gene. The fragment and the ring were further identified as
der(11)(?) and r(11)(?). FISH analysis with probes to PML and RARa were negative for fusion of these loci,
however 88% of cells showed 3 PML signals consistent with a gain of chromosome 15.
Molecular analysis: Negative for FLT3 internal tandem duplication or D835 mutation by PCR. Negative for
t(15;17) PML/RARa by RT-PCR. Negative for t(9;22) BCR/ABL1 by RT-PCR
Proposed diagnosis
Acute myeloid leukemia, not otherwise specified
Interesting feature(s) of the submitted case
The morphologic features of the abnormal neutrophils and blasts, and mostly negative MPO cytochemical
stains. Flow cytometry immunophenotype with expression of myeloid and monocytic markers. Amplification of
MLL on small fragments and ring chromosomes.