Dept. of Cancer Cytogenetics, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai~Dept. of Cancer Cytogenetics, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial
The blast cells expressed HLADR, moderate cCD79, moderate CD19, subset CD10, variable CD22, variable CD15, variable CD34, moderate dim CD123. These cells were dim CD45 negative and negative for CD20, CD14, CD33, CD117, CD163, CD4, CD8, CD11b, CD36, surface CD3, CD5, CD1a, CD56, CD371,CD304, CD13, CD16, CD64, CD11c, CD7, CD2, cytoplasmic CD3, CD27.
GTG
46,XX,t(4;11)(p14;q23),i(7)(q10),t(8;14)(q11.2;q32)[19]/46,XX[1].
Interphase FISH was performed using Vysis LSI KMT2A Dual Color Break Apart Rearrangement Probe (Abbott Molecular, US) and LSI IGH dual color break apart probe (MetaSystems, Altlussheim, Germany).
Interphase FISH showed an abnormal signal pattern for KMT2A indicative for interstitial deletion of the 3' region of KMT2A gene (Figure.A) along with IgH gene rearrangement (Figure.B), in 190 cells of the 200 cells analysed, ISCN: nuc ish(5'KMT2Ax2,3'KMT2Ax1)(5'KMT2A con 3'KMT2Ax1)[190/200] and nuc ish(IGH x2)(5'IGH sep 3'IGHx1)[190/200].
Wysolone (steroid prophase), Vincristine and Daunorubicin (High risk induction chemotherapy), Intrathecal Methotrexate.
Targeted RNA sequencing on a MiSeq platform (Illumina, USA) was performed and KMT2A::PDS5A fusion as a result of translocation between exon 10 of KMT2A gene on chromosome 11 and exon 17 of PDS5A gene on chromosome 4, was identified. This is the first report of pediatric B cell precursor acute lymphoblastic leukemia with KMT2A::PDS5A fusion. PDS5A as a fusion partner of KMT2A has been previously reported in a single case of adult AML associated with stable disease (Put N et.al., 2012). PDS5A is a novel partner of KMT2A in ALL postulated to be involved in DNA damage repair through replication fork protection (Al-Jomah et.al, 2020). This patient also harbored other recurrent chromosomal abnormalities along with KMT2A::PDS5A fusion, such as t(8;14)(q11.2;q32) and i(7)(q10). The t(8;14)(q11.2;q32) is a recurrent translocation associated with intermediate prognosis in B-ALL often with Down syndrome-associated ALL (DS-ALL) likely resulting in IGH::CEBPD fusion and the concomitant overexpression of CEBPD (Akasaka T et.al.,2017 and Messinger YH et.al,2012). Our patient succumbed to induction chemotherapy within 1 month of diagnosis, signifying the inferior outcome associated with this novel partner of KMT2A identified in pediatric B-ALL in conjunction with IgH rearrangement.
No bibliography items were found for this article.
Purvi Mohanty~Dhanlaxmi Shetty~Nikhil Patkar
t(4;11)(p14;q23),KMT2A::PDS5A, in a case of pediatric B acute lymphoblastic leukemia (B-ALL).
Atlas Genet Cytogenet Oncol Haematol. 2023-05-13
Online version: http://atlasgeneticsoncology.org/case-report/209139