A new case of Acute Myeloid Leukemia with semi-cryptic t(7;21)(p22;q22)

Tatiana Gindina, Ildar Barkhatov, Elmira Boychenko, Irina Garbuzova, Maria Vlasova, Elena Nikolaeva, Irina Petrova, Varvara Ovechkina, Tatiana Shorstova Affiliation

I.P. Pavlov State Medical University, R.M. Gorbacheva Memorial Institute of Children Hematology and Transplantation, Cytogenetic Laboratory, Saint Petersburg, Russia (TG, IB, MV, EN, IP, VO, TS); City Children s Hospital No.1, Saint Petersburg, Russia (EB, IG)

Previous history

Preleukaemia

Malignant disease

Inborn condition

Clinics case report

Age

13 yrs

Sex

Liver

Spleen

Lymph nodes

Cns involv

Blood data

Wbc

2,5

11,3

Platelets

278

Blasts

Bone marrow

56 Hypocellular bone marrow, the number of blasts increased up to 56%. Blasts had round shape with a rounded nucleus and looped chromatin structure, with large blue nucleoli. The cytoplasm of blasts was blue and narrow without granularity. Part of the blasts had irregular shape with a bean-shaped nucleus and bright large nucleolus. Their cytoplasm was moderate or abundant, gray-blue with small azurophilic granules. Myelopoiesis: myeloid dysplasia, some cells have giant nuclei, scanty specific granularity, dissociation in the maturation of the nucleus and cytoplasm. Granulocytic population comprised approximately 26% of bone marrow cells. Erythropoiesis was represented by normoblasts. Megakaryocytopoiesis was decreased with hypolobular megakaryocytes.

Cyto path

Cytology

Acute myelomonocytic leukemia (AML), M4

Immunophenotype

Positive for CD45dim, CD33, CD56, CD34, CD7, CD117, CD13, CD71, HLA-DR; additionally, there is abnormal coexpression of CD4 and CD11b.

Rearranged ig tcr

Not performed.

Pathology

Not performed.

Electron microscopy

Not performed.

Precise diagnosis

AML M4 (FAB), AML with multilineage dysplasia (WHO).

Survival data

Date diagnosis

12-2011

Treatment

Induction therapy included AIE (cytarabine/idarubicin/etoposide) and HAM (high-dose cytarabine 3 g/m²/mitoxantrone). Complete remission was achieved after FLAG regimen (fludarabine, cytarabine, granulocyte-colony-stimulating factor) applied as consolidation therapy.

Complete remission

+ Complete hematological and cytogenetic remissions were achieved in April 2012.

Treatment relat death

Relapse

Status

Date last follow

04-2012

Survival

Karyotype

Sample

Bone marrow aspirate.

Culture time

24h, without stimulating agents.

Banding

GTG

Results

Analysis of 20 metaphase cells revealed an abnormal male karyotype. 46,XY,add(21)(q22)[19]/46,XY,idem,del(5)(q13q31)[1].

Mol cytogenet technics

Multicolour fluorescence in situ hybridisation (mFISH) using the 24XCyte Human Multicolor FISH Probe kit (MetaSystems, Germany) and FISH with LSI ETV6(TEL)/RUNX1 (AML1) Dual Color Translocation Probe Set (Abbott Molecular, USA) were performed.

Mol cytogenet results

The semi-cryptic translocation t(7;21) was revealed in all metaphases and split of the RUNX1 gene was detected in the interphase nuclei (three red signals). 46,XY,t(7;21)(p22;q22)[20].ish t(7;21)(RUNX1+;RUNX1+)[20].

Other molec studies

Technics

ASO-PCR, RFLP.

Results

Mutations in NPM1 and FLT3 genes (ITD&D835) were not detected.

Images

G-banded and partial mFISH karyograms showing t(7;21).

Interphase FISH with three signals of RUNX1 (red) and two signals of ETV6 (green) genes.

FISH with LSI ETV6/RUNX1 probe showing the red signals of RUNX1 on der(7) chromosome, der(21) chromosome and on normal chromosome 21. Two normal signals (green) of ETV6 are seen on the chromosomes 12.

Comments section

Comments

Here, we report a new case of AML M4 with semi-cryptic t(7;21)(p22;q22). As known the translocation t(7;21)(p22;q22) is a rare recurrent abnormality in MDS and AML that results in a RUNX1-USP42 fusion as described previously (Paulsson et al., 2006). Although all four patients with t(7;21) revealed a similar cytogenetic lesion, they varied in their clinicopathological features: of the three adults, the first one presented with RAEB-2, the second AML M5, the third AML M0 and the 7-year-old child had AML M0 too. All adults had chemosensitive disease, whereas the child had refractory AML following initial induction therapy and relapsed following allogeneic bone marrow transplantation. Current case of 13-year-old boy diagnosed with acute myelomonocytic leukemia also had evidence of persistent AML after initial course of treatment; he achieved complete hematological and cytogenetic remissions after FLAG.

Call for collab

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Bibliography

Pubmed ID	Last Year	Title	Authors
16357831	2006	A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42.	Paulsson K et al
20064152	2010	Molecular characterisation of a recurrent, semi-cryptic RUNX1 translocation t(7;21) in myelodysplastic syndrome and acute myeloid leukaemia.	Foster N et al
21319259	2011	Microhomologies and topoisomerase II consensus sequences identified near the breakpoint junctions of the recurrent t(7;21)(p22;q22) translocation in acute myeloid leukemia.	Giguère A et al

Citation

Tatiana Gindina, Ildar Barkhatov, Elmira Boychenko, Irina Garbuzova, Maria Vlasova, Elena Nikolaeva, Irina Petrova, Varvara Ovechkina, Tatiana Shorstova

A new case of Acute Myeloid Leukemia with semi-cryptic t(7;21)(p22;q22)

Atlas Genet Cytogenet Oncol Haematol. 2012-04-01

Online version: http://atlasgeneticsoncology.org/case-report/208862/a-new-case-of-acute-myeloid-leukemia-with-semi-cryptic-t(7;21)(p22;q22)