t(6;22)(p21;q11.2) arising at second relapse in a patient with t(8;21)-positive acute myeloid leukemia

Julie C Dueber, Aaron C Shaver, Rebecca S Dean, Amy E Gardner, Stephen Strickland, Mary Ann Thompson, Ashwini Yenamandra  

Department of Pathology, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, USA (JCD, ACS, RSD, AEG, MAT, AY); Department of Medicine, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN 37232, USA (SS)

Previous history

Preleukaemia
+ 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.
Malignant disease
-
Inborn condition
-

Clinics case report

Age
60 yrs
Sex
M
Liver
-
Spleen
-
Lymph nodes
-
Cns involv
-

Blood data

Wbc
7.3
Hb
15.0
Platelets
93
Blasts
0
Bone marrow
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.

Cyto path

Immunophenotype
CD45 dim, CD117+, CD34+, CD13+, CD19-, and CD61+/- myeloblasts.
Rearranged ig tcr
Not performed.
Pathology
Hypercellular bone marrow (60-70%) with focal sheets of CD34+, CD117+ immature cells.
Electron microscopy
Not performed.
Precise diagnosis
Hypercellular bone marrow with trilineage hematopoiesis; extensive involvement by acute myeloid leukemia.

Survival data

Date diagnosis
04-2011
Treatment
History of induction x2; evaluation for initiation of reduced intensity conditioning and/or unrelated stem-cell transplant.
Complete remission
-
Treatment relat death
-
Relapse
+
Phenotype relapse
Current disease represents second relapse.
Status
A
Date last follow
10-2011
Survival
6 status post second relapse and new chromosome abnormality.

Karyotype

Sample
Bone marrow
Culture time
24
Banding
GPW
Results
46,XY,t(8;21)(q22;q22)[5]/46,idem,t(6;22)(p21;q11.2)[3]/46,XY[12]
Karyotype relapse
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.
Mol cytogenet technics
BCR/ABL FISH; AML/ETO FISH.
Mol cytogenet results
200/200 cells assayed negative for BCR rearrangement by FISH. 90/200 cells assayed positive for AML/ETO translocation by FISH.

Other molec studies

Technics
Not performed.
Results
Not performed.

Images

Atlas Image
New abnormal karyotype identified in a subset of the patient s relapsed leukemic disease, 46,XY, t(6;22)(p21;q11.2),t(8;21)(q22;q22), present in 3 of 20 cells.
Atlas Image
FISH probes for BCR (green) and ABL (red) demonstrating no evidence of a rearrangement involving the BCR locus (22q11.2). All 200 cells assayed from the patient s sample at relapse were negative for BCR rearrangement by FISH.
Atlas Image
G-banding (left panel) and FISH (right panel) of the same metaphase spread demonstrating the presence of the BCR locus (green) on chromosome 22 and not chromosome 6.

Comments section

Comments
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.

Bibliography

No bibliography items were found for this article.

Citation

Julie C Dueber, Aaron C Shaver, Rebecca S Dean, Amy E Gardner, Stephen Strickland, Mary Ann Thompson, Ashwini Yenamandra

t(6;22)(p21;q11.2) arising at second relapse in a patient with t(8;21)-positive acute myeloid leukemia

Atlas Genet Cytogenet Oncol Haematol. 2011-11-01

Online version: http://atlasgeneticsoncology.org/case-report/208859/js/lib/cancer-prone-explorer/