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(Paper co-edited with the European LeukemiaNet)
A new case of adult Acute Myeloid Leukemia with t(3;3)(p24;q26)
Written2017-11Bo Yuan, Janice Smith, April Ewton, Sai Ravi Pingali, Arthur Zieske, Amy Breman
Department of Molecular & Human Genetics, Baylor College of Medicine (BY, JS, AB), Houston, TX 77030, USA. Baylor Genetics (BY, JS, AB), Houston, TX 77030, USA,; Department of Pathology & Genomic Medicine, Houston Methodist Hospital (AE, AZ), Houston, TX 77030, USA. Department of Medicine, Houston Methodist Hospital (SRP), Houston, TX 77030, USA.
Age and sex : 68 year(s) old female patient.
Previous History : no preleukemia
no previous malignant disease
no inborn condition of note
Organomegaly : no hepatomegaly ; splenomegaly (acute splenomegaly); no enlarged lymph nodes ; no central nervous system involvement
WBC : 9.13 x 109/L ( RBC: 2.37); Hb : 6.7 g/dL ; platelets : 11 x 109/L; blasts : 5 % .
Cyto pathology classification
Phenotype : AML with a translocation or inversion in chromosome 3; Refractory acute myelogenous leukemia with poor risk cytogenetics, pancytopenia secondary to refractory AML, acute Splenomegaly, fatigue, petechiae, dyspnea on exertion, neutropenic fever, refractory thrombocytopenia with hematuria and persistence of disease.
Immunophenotype : CD34: positive in blasts that account for 45% of cellularity; CD61: positive in megakaryocytes. MPO: Positive in background myeloid cells. Negative in blasts. E-Cadherin and glycophorin: Highlights markedly decreased erythroid precursors
Rearranged Ig Tcr : Not performed
Pathology : The marrow cellularity is approximately 90% (biopsy/clot); Erythroid elements: Markedly decreased number. Normoblastic; Myeloid elements: Left shifted with increased blasts. Blasts account for 18% of cells in the dilute aspirate and about 45 of cells in the CD34 immunostained biopsy. Eosinophilia is seen on biopsy specimen; Megakaryocytes: Markedly increased in number with clustering and markedly dyspoietic morphology (small hypolobulated, dysjointed nuclei, hyperlobed); Reticulin stain shows Grade 1 fibrosis.
Electron microscopy : Not performed
Precise diagnosis : Acute myelogenous leukemia
Date of diagnosis: 02-2017
Treatment : Reduced dose of anthracycline therapy due to cardiac function; Cytarabine and idarubicin; Dacogen; Nivolumab; Decitabine; Hydroxyurea
Complete remission : None
Treatment related death : -
Relapse : -
Status : Alive 05-2017
Survival : 3 month(s)
Sample : Bone marrow ; culture time : 24 h, and 48 hours unstimulated cultures ; banding : GTG banding
Results : 45,XX,t(3;3)(p24;q26),-7[20]
Other molecular cytogenetics technics : Fluorescence in situ Hybridization (FISH)
Other molecular cytogenetics results : Confirmatory FISH using the Cytocell EVI1 Breakapart Probe (REF: LPH 036-A / LPH 036-A50) was performed on cells harvested from 24 hour bone marrow culture. The FISH probe mixture consists of a 156 kb probe telomeric to the D3S4415 marker including the LRRC34 gene (red, R), a 179 kb probe including the entire EVI1 (MECOM) gene plus flanking regions (green, G), and a 559 kb probe centromeric to the EVI1 gene including the D3S3364 marker (aqua, A), all within the 3q26.2 region. Interphase cells showed a 1R/1GA/1RGA signal pattern, corresponding to one split red/green signal with the aqua signal remaining with the green signal, confirming the translocation breakpoint between the EVI1 and LRRC34 genes (Figure 2). However, the partner of EVI1 resulting from the translocation remains unknown.
Karyotype of the cell line demonstrating the t(3;3)(p24;q26) and loss of a copy of chromosome 7 (red arrows). The lower panel shows the abnormal chromosomes 3 at increasing band resolution.
FISH using the Cytocell EVI1 Breakapart Probe demonstrating the breakpoint at 3q26.2 between EVI1 and LRRC34, a gene telomeric to EVI1, in both interphase (A) and metaphase cells (B).
Rearrangements involving the 3q26 region have been described in up to 10% of acute myeloid leukemias (AML), chronic myeloid leukemias in blast crisis (CML BC), and myelodysplastic syndrome (Poppe 2006). The most common rearrangement is a paracentric inversion of the long arm, inv(3)(q21q26), although multiple rearrangements of this region have been described (Huret 2005, Jancuskova 2014, Lawce 2017). While the breakpoints are variable and may include translocations, inversions or other structural complexities, they unanimously result in EVI1 overexpression. Interphase FISH assays have been used to detect rearrangements involving the EVI1 locus at 3q26 (Wieser 2003). Monosomy 7 is also frequently present, and is associated with a poorer prognosis (Haferlach 2012, Huret 2005, Lugthart 2010). While multiple partners have been identified for EVI1, the partner of EVI1 in rearrangements involving 3p24 and 3q26 is unknown. Similar to the current case, a pericentric inversion involving both the short and long arms of chromosome 3, inv(3)(p24q26), has been reported in ten cases (Haferlach 2012), with elevated EVI1 expression reported. Therefore, identification of the partner gene warrants further investigation.
Internal links
Atlas Cardt(3;3)(p24;q26) ?/MECOM
Three novel cytogenetically cryptic EVI1 rearrangements associated with increased EVI1 expression and poor prognosis identified in 27 acute myeloid leukemia cases
Haferlach C, Bacher U, Grossmann V, Schindela S, Zenger M, Kohlmann A, Kern W, Haferlach T, Schnittger S
Genes Chromosomes Cancer 2012 Dec;51(12):1079-85
PMID 22887804
Molecular characterization of the rare translocation t(3;10)(q26;q21) in an acute myeloid leukemia patient
Jancuskova T, Plachy R, Zemankova L, Hardekopf DW, Stika J, Zejskova L, Praulich I, Kreuzer KA, Rothe A, Othman MA, Kosyakova N, Pekova S
Mol Cytogenet 2014 Jul 15;7:47
PMID 25071866
3q21q26 rearrangements in treatment related leukemia
Jean-Loup Huret
Atlas Genet Cytogenet Oncol Haematol. 2005;9(3):234-235. 3q21q26 rearrangements in treatment related leukemia
MECOM (EVI1) Rearrangements: A Review and Case Report of Two MDS Patients with Complex 3q Inversion/Deletions
Lawce H, Szabo E, Torimaru Y, Davis C, Osterberg K, Olson S, Moore S
J Assoc Genet Technol 2017;43(1):9-14
PMID 28459701
Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26
Lugthart S, Gröschel S, Beverloo HB, Kayser S, Valk PJ, van Zelderen-Bhola SL, Jan Ossenkoppele G, Vellenga E, van den Berg-de Ruiter E, Schanz U, Verhoef G, Vandenberghe P, Ferrant A, Köhne CH, Pfreundschuh M, Horst HA, Koller E, von Lilienfeld-Toal M, Bentz M, Ganser A, Schlegelberger B, Jotterand M, Krauter J, Pabst T, Theobald M, Schlenk RF, Delwel R, Döhner K, Löwenberg B, Döhner H
2)/t(3;3)(q21;q26 2) and various other 3q abnormalities in acute myeloid leukemia
PMID 20660833
EVI1 is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements
Poppe B, Dastugue N, Vandesompele J, Cauwelier B, De Smet B, Yigit N, De Paepe A, Cervera J, Recher C, De Mas V, Hagemeijer A, Speleman F
Genes Chromosomes Cancer 2006 Apr;45(4):349-56
PMID 16342172
Interphase fluorescence in situ hybridization assay for the detection of rearrangements of the EVI-1 locus in chromosome band 3q26 in myeloid malignancies
Wieser R, Schreiner U, Rieder H, Pirc-Danoewinata H, Grüner H, Loncarevic IF, Fonatsch C
Haematologica 2003 Jan;88(1):25-30
PMID 12551823


This paper should be referenced as such :
Yuan B, Smith J, Ewton A, Pingali SR, Zieske A, Breman A
A new case of adult Acute Myeloid Leukemia with t(3;3)(p24;q26)
Atlas Genet Cytogenet Oncol Haematol. in press
On line version :

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