t(1;21)(p22;q22) RUNX1/CLCA2

2012-06-01   Amélie Giguçre , Josée Hébert 

1.Quebec Leukemia Cell Bank, Division of Hematology-Oncology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, H1T 2M4, Canada

Clinics and Pathology


Two AML cases positive for the t(1;21)(p22;q22) were reported, a 9 year-old boy (Nadal et al., 2008) and a 64 year-old man (Giguère and Hébert, 2010).


The 9 year-old boy presented in September 2004 with an initial diagnosis of acute myeloid leukemia with maturation (AML-M2) with a normal karyotype. In December 2004, he underwent an allogeneic bone marrow transplantation and then relapsed in June 2006. At relapse, the karyotype was 46,XY,t(1;21)(p22;q22)[15]/46,XX[5].
The adult patient developed a de novo AML-M2 with an abnormal karyotype 45,XY,-7[17]/46,XY[3] in December 2005. He received a standard induction and consolidation chemotherapy followed by an allogeneic hematopoietic stem cell transplantation. In August 2007, he developed a t(1;21)(p22;q22) positive t-AML. Complete blood count showed a white blood cell count of 16.4 x 109/L, hemoglobin of 86 g/L and platelet count of 34 x109/L. The bone marrow aspirate showed 52% of blast cells.


The pediatric patient was treated with cytarabine, mitoxantrone and amsacrine. At complete remission, he underwent an allogeneic stem cell transplantation with a conditioning regimen including etoposide and total body irradiation. At relapse, the boy underwent a second bone marrow transplantation.
The adult patient was treated with a standard induction chemotherapy regimen (infusional cytarabine combined with daunorubicine) and two cycles of consolidation therapy with high doses cytarabine, followed by a reduced intensity allogeneic stem cell transplantation. The t(1;21) positive t-AML was not treated with chemotherapy. The patient received palliative care.


The boy was alive in April 2012 (Nadal, personal communication). The adult patient died one month and 18 days following t-AML development.




FLT3-ITD (FLT3 internal tandem duplication) mutation was detected in the pediatric patients leukemic cells and was absent in the adult patients cells.


Cytogenetics morphological

Can be easily identified using G-banded chromosomes.

Cytogenetics molecular

FISH using the RUNX1-RUNX1T1 probe showed splitted signals located on derivative chromosomes 1 and 21. RUNX1 rearrangement was confirmed using the RP11-299D9 BAC probe (BACPAC Resources Center) (Giguère and Hébert, 2010).
Atlas Image
Metaphasic FISH using the LSI RUNX1-RUNX1T1 dual color translocation probe (Abbott Molecular). Three green signals (21q22, RUNX1 gene) are shown (arrows), indicating the presence of a RUNX1 rearrangement. Two normal red signals (8q22, RUNX1T1 gene) were observed.

Additional anomalies

The t(1;21) was the sole anomaly in t-AML cells.

Genes Involved and Proteins

Gene name
RUNX1 (runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene))
Dna rna description
The RUNX1 gene contains 8 coding exons spanning 260 kilobases (kb) of genomic DNA. Transcription orientation: telomere to centromere.
Atlas Image
The RUNX1 gene and protein are represented. Exons 3 to 5 code for the DNA binding Runt homology domain (RHD) whereas exons 7 and 8 encode the transcriptional regulatory domain which includes activation (TA) and inhibitory domains (ID).
Protein description
RUNX1 is a conserved member of the RUNX family and is a master regulator of hematopoiesis through activation or repression of lineage-specific genes.
Gene name
CLCA2 (chloride channel accessory 2)
Dna rna description
The CLCA2 gene contains 14 exons which spans 32 kb of genomic DNA. Transcription orientation: telomere to centromere.
Atlas Image
The CLCA2 gene and protein are represented. The calcium-activated chloride channel (CLCA), the von Willebrand factor type A domain (VWA) and a domain of unknown function (DUF1973) are encoded by amino acids 8 to 265, 312 to 470 and 494 to 674 respectively, according to the PFAM website (http://pfam.sanger.ac.uk).
Protein description
CLCA2 is a member of the calcium-activated chloride channel family. The protein was proposed to function as a regulator of chloride current and to act as a potential tumor suppressor in breast cancer cells (Gruber and Pauli, 1999; Elble and Pauli, 2001).

Result of the Chromosomal Anomaly

Atlas Image
Main fusion transcript resulting in a fusion of RUNX1 exons 1-6 to CLCA2 exons 2-14.


5 RUNX1-CLCA2 3.


At least six out-of-frame fusion transcripts were identified (Giguère and Hébert, 2010).


In this case, RUNX1-CLCA2 fusion transcripts lead to truncated RUNX1 proteins (Giguère and Hébert, 2010).

Highly cited references

Pubmed IDYearTitleCitations
208758712010CLCA2, a novel RUNX1 partner gene in a therapy-related leukemia with t(1;21)(p22;q22).3


Pubmed IDLast YearTitleAuthors
114836092001Tumor suppression by a proapoptotic calcium-activated chloride channel in mammary epithelium.Elble RC et al
208758712010CLCA2, a novel RUNX1 partner gene in a therapy-related leukemia with t(1;21)(p22;q22).Giguère A et al
105540241999Tumorigenicity of human breast cancer is associated with loss of the Ca2+-activated chloride channel CLCA2.Gruber AD et al
182065482008RUNX1 rearrangements in acute myeloblastic leukemia relapsing after hematopoietic stem cell transplantation.Nadal N et al


Fusion gene

RUNX1/CLCA2 RUNX1 (21q22.12) CLCA2 (1p22.3) M t(1;21)(p22;q22)|RUNX1/CLCA2 RUNX1 (21q22.12) CLCA2 (1p22.3) TIC
Atlas Image
Partial GTG-banded karyotype showing derivative chromosomes 1 and 21 involved in the t(1;21)(p22;q22).


Amélie Giguçre ; Josée Hébert

t(1;21)(p22;q22) RUNX1/CLCA2

Atlas Genet Cytogenet Oncol Haematol. 2012-06-01

Online version: http://atlasgeneticsoncology.org/haematological/1608/t(1;21)(p22;q22)