-

-

-

+ Patient diagnosed with breast cancer in 1995, treated with adjuvant chemotherapy consisting of 4 cycles of CAF (cyclophosphamide, doxorubicin and fluorouracil) and CMF (cyclophosphamide, methotrexate and fluorouracil) followed by tamoxifen for 6 years. On 6/2006, she had evidence of recurrence and subsequent liver, ribs, and skull metastases. She was treated with several other chemotherapies such as taxotere, gemzar, fluvestrant, taxol, bevacizumab and xeloda, and radiation therapy. On 11/2011, she developed brain metastasis and was successfully treated with gamma knife. Over her last year, she was on oral cyclophosphamide and doxorubicin.

Family History: Sister with brain tumor and brother with colon cancer.

59 yrs

F

-

-

-

+ brain metastasis

58.7

8.7

47

Bone marrow biopsy revealed a hypercellular marrow with 80% cellularity, multilineage dysplasia, 10.2% immature monocytes and 3.2% myeloblasts. CD34/CD117 showed approximately 10% immature myeloid/monocytic cells. CD64 highlighted the expanded monocytic component. In addition there were scattered metastatic tumor cells positive for AE1/AE3, mammoglobin and BRST1 by immunohistochemistry supporting primary breast origin.

Therapy related myeloid neoplasm best classified as therapy related myelodysplastic /acute myeloid leukemia (t-MDS/AML).

Flow cytometric of peripheral blood detected 2% myeloblasts expressing CD13, CD33, CD 34, CD117 and HLA-DR, and partially expressing CD14, CD4, CD11d, CD11c and CD64. In addition there were two monocytes gates detected; 18% monocytes were expressing CD13, CD33, and partially expressing CD4, CD11b, CD11c, CD15, CD117, CD64 and CD14. There was a subpopulation of monocytes representing 6% of gated monocytes were negative CD14, CD19, CD2, CD10, CD7, CD34, CD163 but HLA-DR positive.

Not performed.

Not performed.

Therapy related MDS/AML

01-2013

Only supportive therapy

-

-

-

D

02-2013

0,5

Progressed quickly, expired shortly after diagnosis due to lactic acidosis and hypotention

Bone marrow aspirate

24 unstimulated culture and 48 hrs culture with 10% conditioned medium

GTG

46, XX,t(2;11)(q31;p15)[14]/47,XX,t(2;11)(q31;p15),+8[6] (Figure 1)

In addition, dual color FISH using Signature Genomic DNA probes Rp11-387A1/2q31.1 covering HOXD gene cluster including both HOXD11 and HOXD13 genes was labeled SpectrumOrange, while the RP11-120E20/11p15.4 covering NUP98 gene was labeled SpectrumGreen (PerkinElmer, Spokane, WA). The hybridization revealed a fusion signal located on der(2) due to a translocation of NUP98/15p15 (green) to HOXD/2q31(orange) gene region (Figure 2). The remainder of HOXD signal was translocated to 11p15.

In Summary, t(2;11)(q31;p13) translocation in leukemia is rare but recurrent, and occurs in de novo AML as well as t-MDS/AML, and six out eight of patients were <15 years including three infants (Table 1). Morphologically this translocation appears to be associated with monocytic features, mostly AML M4. The t(2;11) leads to the generation of leukemogenic NUP98 fusion protein.