-

-

+ Thalassemia trait carrier

17 yrs

F

+

+

+

-

138.7

6.9

51

76

100 Bone marrow biopsy was hypercellular (100%) and replaced by myeloblasts and monoblasts. Normal hematopoiesis was greatly decreased and there was prominent hemophagocytosis. The majority of the blasts were myeloperoxidase positive however another smaller component of blasts was nonspecific esterase positive

Acute myeloid leukemia with abnormal eosinophils (AML-M4eos)

Flow cytometry of bone marrow aspirate identified a significant population of myeloblasts (49%) expressing CD34, HLA-DR, CD9, CD13, CD33, CD117 and partially expressing CD15, CD11b, and CD64. A second population of monocytes is also identified (37%) expressing CD4, CD14, CD15, CD36 and CD64.

Not performed.

Bone marrow aspirate revealed myeloblasts, monoblasts, monocytes, and increased eosinophils many of which had abnormal granules (FAB AML-M4eos).

Not performed.

Acute myelomonocytic leukemia with abnormal eosinophils (AML-M4eos) and CBFB/16q22 rearrangement.

03-2011

Intrathecal methotrexate, hydrocortisone, and cytarabine.

+

-

-

A

09-2011

6

Bone marrow

24 without stimulating agents and 48 hrs with 10% conditioned medium

GTG

At time of diagnosis abnormal metaphase cells with the following karyotype was found; 46,XX,ins(16)(q22p13p13)[20] (see Figure 1). Remission bone marrow on 4/20/2011 and 9/13/2011 revealed a normal female karyotype; 46,XX[20].

Fluorescence in situ hybridization (FISH) using LSI CBFB dual color break-apart rearrangement DNA probes (Abbott Molecular IL, USA), and CBFB/MYH11 dual fusion translocation DNA probe (Cytocell Inc. Cambridge, UK) were performed.

The hybridization with the CBFB break-apart probe produced a split pattern in 62% of interphase cells. On metaphase cells, the 5 CBFB (SepctrumRed) and 3 CBFB (SepctrumGreen) signals stayed on the 16q, instead of 5 CBFB being relocated to 16p as seen in the standard inv(16). The CBFB signals were separated but maintained the orientation pattern of the 5 and 3 probe, suggesting they were split by an insertion (Figure 2A). Subsequently, using the CBFB-MYH11 probe on metaphases showed that MYH11 signal on 16p moved and juxtaposed to CBFB on 16q, confirming the insertion of MYH11 into CBFB (Figure 2B).

The CBFB/MYH11 gene fusion is strongly associated with AML-M4 with abnormal eosinophils. Generally, the fusion is generated from inv(16)(p13q22) or t(16;16) with the inversion being much more common than translocation (Le Beau et al., 1983; Tobal et al., 1995). The case presented here demonstrates that insertion is another mechanism in producing CBFB/MYH11 gene fusion in AML-M4eos. To our best knowledge, there is only one reported case of AML-M4 having similar structural abnormality of chromosome 16 and CBFB/MYH11 fusion (O Reilly et al., 2000). These two cases suggest that insertion represents a variant rare rearrangement for the formation of this fusion. FISH is highly recommended to characterize unusual abnormalities of chromosome 16 and to confirm the CBFB-MYH11 fusion.