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(Paper co-edited with the European LeukemiaNet)
t(6;17)(p21;p13) and acquisition of the Philadelphia chromosome translocation with p190 BCR-ABL1 transcript during the course of myelodysplastic syndrome
Written2018-01Adriana Zamecnikova
Kuwait Cancer Control Center, Kuwait
Age and sex : 47 year(s) old male patient.
Previous History : preleukemia (The patient had thrombocytopenia for 10 years (platelet counts ranged between 70x106/L to 130x106/L, for what he had never received any treatment.)
no previous malignant disease
no inborn condition of note
Organomegaly : no hepatomegaly ; no splenomegaly ; no enlarged lymph nodes ; no central nervous system involvement
WBC : 2.5 x 109/L ; Hb : 8.6 g/dL ; platelets : 6 x 109/L; blasts : 43 % .
Bone marrow : The bone marrow was hypocellular with 6.5% blasts at presentation. 7 months later, the patient MDS transformed to AML and his bone marrow biopsy showed markedly hypercellular marrow with 69% blasts (0.4% promyelocytes, 2.7% myelocytes, 1.1% neutrophils, 1.8% lymphocytes and 25% erythroblasts).
Cyto pathology classification
Phenotype : Acute myeloid leukemia without maturation
Immunophenotype : Myeloid immunophenotype, (positive for CD13, CD33, CD34, HLDR, CS45 and CD117) with aberrant expression of CD7.
Precise diagnosis : AML with myelodysplasia-related changes. Provisional entity: AML with BCR/ABL1
Date of diagnosis: 08-2011
Treatment : After the patient was diagnosed with MDS, therapy with decitabine was administrated but the patient remained cytopenic. At progression chemotherapy combined with imatinib (400 mg/day) was administrated that was escalated to 800 mg/day two weeks later.
Complete remission : None
Status : Alive 04-2012
Survival : 7 month(s)
Sample : bone marrow ; culture time : 24 h ; banding : G-banding
Results : 47,XY,t(6;17)(p21;p13),+8 [10]/46,XY [10] at presentation; 47,XY,t(6;17)(p21;p13),+8,t(9;22)(q34;q11)[18]/48,XY,t(6;17)(p21;p13),+8,t(9;22)(q34;q11),+10 [2]/46,XY [20 ] at transition
Other molecular cytogenetics technics : Fluorescence in situ hybridization studies (FISH) were performed on slides prepared for cytogenetic analysis using a t(9;22) specific BCR/ABL dual color, dual fusion, CEP 8 and LSI P53 probes (Abott Molecular/Vysis, US).
Other molecular cytogenetics results : Breakpoint on 17p13 prompted us to search for deletion of the p53 gene at presentation; however fluorescence in situ hybridization with LSI p53 probe revealed only the presence of 2 normal P53 signals in 500 interphase cells. Hybridization with chromosome 8 centromeric probe showed extra chromosome +8 in 50 % of cells. FISH studies with BCR/ABL performed at transition revealed 60% positive cells while retrospective studies performed on stored bone marrow cells from MDS phase failed to detect either the Philadelphia chromosome, either the BCR/ABL1 rearrangement.
Other molecular studies
technics : Molecular studies were performed from total RNA extracted from the bone marrow sample using the TriZol LS reagent (Invitrogen, US) according to the manufacturer's recommendations. cDNA was prepared from 2μg of total RNA with the Superscript II cDNA Synthesis Kit (Invitrogen, US) according to manufacturer's instructions.
results : Quantitative molecular studies performed with GeneXpert (Cepheid, US) were negative for the major BCR/ABL1 transcript. The absence of p210 BCR-ABL1 transcript was confirmed by reverse transcription-polymerase chain reaction analysis; however it showed breakpoint cluster region rearrangement between exons e1 and a2, compatible with the minor p190 BCR/ABL1 transcript.
Figure 1. Karyotype of the patient from the time of diagnosis showing the 47,XY,t(6;17)(p21;p13),+8.
Figure 2. (A) Representative metaphase of the patient from the time of transition showing the 47,XY,t(6;17)(p21;p13),+8,t(9;22)(q34;q11) karyotype. (B) Fluorescence in situ hybridization with LSI BCR-ABL1 probe (Vysis, IL, US) showing the fusion BCR-ABL1 signal on der(9) and der(22) chromosomes. (C) Ethidium-bromide-stained agarose gel showing RT-PCR-amplified BCR-ABL1 chimaeric transcripts1. Lanes M, molecular weight marker; lane 1, e1a2 fusion in a patient; line 2, ABL internal control; line 3, e1a2-positive cell control; line 4, negative control; line 5, negative reaction with p210BCR/ABL primers in a patient; line 6, p210 CML positive control.
We described a rare t(6;17)(p21;p13) (La Starza et al., 26) in a patient diagnosed with myelodysplastic syndrome that terminated in AML associated with acquisition of the Philadelphia chromosome translocation and the p190 BCR-ABL1 transcript. The patient initially had thrombocytopenia for 10 years, but developed MDS and at that time karyotyping revealed the chromosomal translocation t(6;17)(p21;p13) associated with an extra chromosome 8. The initial myelodysplastic syndrome terminated to acute myeloid leukemia, accompanied by an appearance of a new clone, characterized by a Philadelphia chromosome. Reverse transcription-polymerase chain reaction analysis further revealed the presence of the minor p190 BCR-ABL1 transcript. Developing a Philadelphia chromosome, considered a primary anomaly, during the course of MDS is extremely rare phenomenon, described only in few patients (Melo et al., 1994; Onozawa et al., 2003; Advani et al., 2004; Keung et al., 2004). Our study illustrates that the Ph translocation may develop from an existing MDS clone, accompanying or perhaps inducing disease transformation. The availability of preleukemic MDS phase in our patient offers an unique opportunity to analyze the role of BCR-ABL1 in leukemogenesis and the evolution of leukemia clones in hematological malignancies.
Internal links
Atlas Cardt(6;17)(p21;p13)
Case Reportt(6;17)(p21;p13) associated with t(3;3)(q21;q26.2) in AML
Philadelphia chromosome positive myelodysplastic syndrome and acute myelogenous leukemia.
Advani AS.
Leuk Res 2004 Jun;28(6):545-6.
PMID 15120928
Philadelphia chromosome positive myelodysplastic syndrome and acute myeloid leukemia-retrospective study and review of literature.
Keung YK, Beaty M, Powell BL, Molnar I, Buss D, Pettenati M.
Leuk Res 2004 Jun;28(6):579-86.
PMID 15120934
Genomic gain at 6p21: a new cryptic molecular rearrangement in secondary myelodysplastic syndrome and acute myeloid leukemia.
La Starza R, Aventin A, Matteucci C, Crescenzi B, Romoli S, Testoni N, Pierini V, Ciolli S, Sambani C, Locasciulli A, Di Bona E, Lafage-Pochitaloff M, Martelli MF, Marynen P, Mecucci C
Leukemia 2006 Jun;20(6):958-64.
PMID 16617324
P190BCR-ABL chronic myeloid leukaemia: the missing link with chronic myelomonocytic leukaemia?
Melo JV, Myint H, Galton DA, Goldman JM.
Leukemia 1994 Jan;8(1):208-11.
PMID 8289491
A case of myelodysplastic syndrome developed blastic crisis of chronic myelogenous leukemia with acquisition of major BCR/ABL.
Onozawa M, Fukuhara T, Takahata M, Yamamoto Y, Miyake T, Maekawa I.
Ann Hematol 2003 Sep;82(9):593-5.
PMID 12898186


This paper should be referenced as such :
Zamecnikova A
t(6;17)(p21;p13) and acquisition of the Philadelphia chromosome translocation with p190 BCR-ABL1 transcript during the course of myelodysplastic syndrome
Atlas Genet Cytogenet Oncol Haematol. in press
On line version :

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