+ The patient was diagnosed with FLT3 negative, NMP1 negative AML in March of 2010. His karyotype at diagnosis was 46,XY, t(8;21)(q22;q22). He was treated with cytarabine and idarubicin for induction and cytarabine and daunorubicin for consolidation. He relapsed in November, 2010 and received mitoxantrone, etoposide, and cytarabine for re-induction. Cytogenetics performed at the time of this first relapse continued to demonstrate t(8;21)(q22;q22) as the sole cytogenetic abnormality. Upon evaluation in April, 2011 for potential stem-cell transplant, the bone marrow biopsy described in this study confirmed that the patient s acute myeloid leukemia had relapsed for a second time.

-

-

60 yrs

M

-

-

-

-

7.3

15.0

93

0

60 Hypercellular bone marrow (60-70%) with extensive involvement by leukemia. Histologic sections demonstrate focal sheets of CD34+, CD117+ immature cells. The blasts identified on histologic sections of the marrow are under-represented on the aspirate, which shows 1% blasts, and the flow cytometry specimen, which demonstrates 3% CD45 dim, CD117+, CD34+, CD13+, CD19-, and CD61- myeloblasts. This immunophenotype is consistent with the patient s previous leukemic blasts.

CD45 dim, CD117+, CD34+, CD13+, CD19-, and CD61+/- myeloblasts.

Not performed.

Hypercellular bone marrow (60-70%) with focal sheets of CD34+, CD117+ immature cells.

Not performed.

Hypercellular bone marrow with trilineage hematopoiesis; extensive involvement by acute myeloid leukemia.

04-2011

History of induction x2; evaluation for initiation of reduced intensity conditioning and/or unrelated stem-cell transplant.

-

-

+

Current disease represents second relapse.

A

10-2011

6 status post second relapse and new chromosome abnormality.

Bone marrow

24

GPW

46,XY,t(8;21)(q22;q22)[5]/46,idem,t(6;22)(p21;q11.2)[3]/46,XY[12]

Analysis of bone marrow specimen after 1 additional month of therapy (May 2011) demonstrates the persistence of the 46,XY,t(6;22)(p21;q11.2),t(8;21)(q22;q22) karyotype in 7 out of 20 cells assayed. Morphologic interpretation of this biopsy specimen indicates continued progression of disease.

BCR/ABL FISH; AML/ETO FISH.

200/200 cells assayed negative for BCR rearrangement by FISH. 90/200 cells assayed positive for AML/ETO translocation by FISH.

Not performed.

Not performed.

Although AML1-ETO t(8;21)(q22;q22) is a well-described cytogenetic anomaly in AML, the t(6;22)(p21;q11.2) seen in this patient s relapse is much more unusual. Few cases have been previously described (Huret, 2010), and only as anecdotal reports in CML, pre-B ALL, and CLL. This is the first reported case of t(6;22)(p21;q11.2) in a patient with AML. Notably, FISH studies targeting the BCR locus (22q11.2) did not reveal evidence of rearrangement, indicating that BCR is not involved in this (6;22) translocation. The appearance of the (6;22) translocation in the background of the patient s previous cytogenetic abnormality indicates clonal evolution of this progressing acute myeloid leukemia. This pattern of clonal evolution is particularly interesting in light of the patient s somewhat aggressive clinical course, unusual in t(8;21) AML.