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(Paper co-edited with the European LeukemiaNet)
t(4;11)(q23;p15) in paediatric early T cell precursor acute lymphoblastic leukemia.
Written2018-03Anurag Gupta, Sirisharani Siddaiahgari, Nagaraju Nalla, Mukkanteeswara Rao Kasaragadda, Manu Goyal
Department of Hematopathology and Genetics, AMPATH, Nallagandla, Serilingampally Hyderabad, Telangana, India 500019 (AG, NN, MRK, MG); Department of Paediatric Oncology, Rainbow Children's Hospital, Karvy Lanes, Banjara Hills, Hyderabad, Telangana, India - 500 034 (SS);
Age and sex : 12 year(s) old female patient.
Previous History : no preleukemia
no previous malignant disease
no inborn condition of note
Organomegaly : hepatomegaly (3 cms below right costal margin); splenomegaly (3 cms below left costal margin); enlarged lymph nodes (Cervical lymphadenopathy); no central nervous system involvement
WBC : 1.49 x 109/L ; Hb : 6.6 g/dL ; platelets : 1.9 x 109/L; blasts : 2 % .
Bone marrow : 30%; Hypocellular and aparticulate bone marrow aspirate smears and show presence of 30% blasts.
Cyto pathology classification
Phenotype : L1
Immunophenotype : The blast cells were dim CD45 positive and expressed moderate CD34, CD38, CD7, CD33, dim CD2, partially CD117 and dim cytoplasmic CD3. These cells are negative for CD19, CD10, CD20, HLADR, CD4, CD8, surface CD3, CD5 and CD1a.
Rearranged Ig Tcr : Not done
Pathology : Acute lymphoblastic leukemia
Electron microscopy : Not done
Precise diagnosis : Early T cell precursor Lymphoblastic leukemia.
Date of diagnosis: 12-2015
Treatment : High risk BFM 95
Complete remission was obtained
Treatment related death : -
Relapse : -
Status : Alive 11-2017
Survival : 24 month(s)
Sample : Bone marrow aspirate ; culture time : 17 h, overnight with and without colcemid ; banding : GTG
Results : 46,XX,t(4?11)(q23?p15)[09]/46,XX[11]
Other molecular cytogenetics technics : Fluorescence in situ hybridisation was done on bone marrow culture pellet using NUP98 break apart probe, Zytovysion, Fischai, Bremerhaven, Germany.
Other molecular cytogenetics results : Positive for rearrangement of the NUP98 gene in 34% of the cells.
Other findings
results : Negative for BCR/ABL1 fusion, ETV6/RUNX1 fusion, KMT2A gene rearrangement and E2A gene rearrangement by FISH.
Figure 1: Karyogram showing t(4;11)(q23?p15) GTG staining and banding method × 100 oil immersion, Carl Zeiss Axios cope and processed using IKAROS software)
Figure 2: FISH using NUP98 break apart probe, Zytovysion, Fischai, Bremerhaven, Germany.
The t(4;11)(q23;p15) is a rare recurrent translocation in T cell acute lymphoblastic leukemia (T cell ALL) that has been described in ten cases till date and leads to the fusion of NUP98 gene and RAP1GDS1 gene (Mohamed AN, In press). The uniqueness of this translocation is it not involving the T cell receptor genes. It has previously been associated with T cell lymphoblastic leukemias arising from progenitor cells aberrantly expressing myeloid molecules (Mecucci, C., 2000). In the present case this translocation was detected in early precursor T cell lymphoblastic leukemia (EPT-ALL), a recently described sub entity of T cell ALLs associated with inferior outcome that is characterised by CD1a negative, CD8 negative, CD5 weak, aberrant expression of myeloid and or stem cell antigens like CD117 CD13 and CD33 (Coustain S., 2009). Although the previous published three case reports described aberrant myeloid antigen expression, none were reported with CD117 expression. Nine cases were of adults while a single case was described in 6 years old female. The translocation was detected at diagnosis in eight cases and was associated with additional abnormalities in three cases. In one case it was cytogenetically cryptic and was detected by molecular studies (Cimino G., 2001). The t(4;11) is associated with unfavourable outcome (Mohamed AN, In press). All the described cases died of the disease except a 6 years old female child who remained alive after 25 months of follow up (Pui CH., 1991). The present case was of EPTALL with t(4;11) who is alive and remains in remission 24 months post diagnosis. It is postulated that t(4;11) may impart unfavourable prognosis in adults rather than paediatric population; however, further studies are warranted.
ACKNOWLEDGEMENTS: The authors wish to acknowledge Ms. Emily-Jane Rüschendorf and her scientific team at Zytovysion, Fischai, Bremerhaven, Germany for their support in performing FISH for NUP98 on this case.
Internal links
Atlas Cardt(4;11)(q23;p15) NUP98/RAP1GDS1
Chromosomal abnormalities identify high-risk and low-risk patients with acute lymphoblastic leukemia
Bloomfield CD, Goldman AI, Alimena G, Berger R, Borgström GH, Brandt L, Catovsky D, de la Chapelle A, Dewald GW, Garson OM, et al
Blood 1986 Feb;67(2):415-20
PMID 3455828
Molecular evaluation of the NUP98/RAP1GDS1 gene frequency in adults with T-acute lymphoblastic leukemia
Cimino G, Sprovieri T, Rapanotti MC, Foà R, Mecucci C, Mandelli F
Haematologica 2001 Apr;86(4):436-7
PMID 11325654
Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia
Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, Cheng C, Su X, Rubnitz JE, Basso G, Biondi A, Pui CH, Downing JR, Campana D
Lancet Oncol 2009 Feb;10(2):147-56
PMID 19147408
A variant translocation between chromosomes 4 and 11, t(4q;11p) in a child with acute leukemia
Inoue S, Tyrkus M, Ravindranath Y, Gohle N
Am J Pediatr Hematol Oncol 1985 Summer;7(2):211-4
PMID 3842567
t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes: characterization of a new subset of T acute lymphoblastic leukaemia
Mecucci C, La Starza R, Negrini M, Sabbioni S, Crescenzi B, Leoni P, Di Raimondo F, Krampera M, Cimino G, Tafuri A, Cuneo A, Vitale A, Foà R
Br J Haematol 2000 Jun;109(4):788-93
PMID 10929031
t(4;11)(q23;p15) NUP98/RAP1GDS1
Mohamed AN.
Atlas Genet Cytogenet Oncol Haematol. in press
Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23): a collaborative study of 40 cases
Pui CH, Frankel LS, Carroll AJ, Raimondi SC, Shuster JJ, Head DR, Crist WM, Land VJ, Pullen DJ, Steuber CP, et al
Blood 1991 Feb 1;77(3):440-7
PMID 1991161
[Optimal Medical Therapy and Secondary Prevention in Patients after an Acute Coronary Syndrome]
Stähli BE, Landmesser U
Dtsch Med Wochenschr 2018 May;143(9):672-679
PMID 29684934


This paper should be referenced as such :
Gupta A, Siddaiahgari S, Nalla N, Rao Kasaragadda M, Goyal M.
t(4;11)(q23;p15) in paediatric early T cell precursor acute lymphoblastic leukemia.
Atlas Genet Cytogenet Oncol Haematol. in press
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indexed on : Wed Nov 13 22:52:05 CET 2019

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