T-Acute lymphoblastic leukemia/lymphoma

In two cases T-ALL was arrested at cortical stage. In the other 3 patients, immunophenotype was incomplete or not available [Brandimarte et al, 2013, 2014].

t(X;10)( p11;p12) DDX3X/MLLT10 occurs in approximately 3% of adult T-ALL and characterizes a subgroup of NOTCH1 positive leukemias.
All five T- ALL patients were males aged 11 - 38 years (median 24.4 years).

Pts	Age, gender	WBC (x109/l)	Immuno-phenotype	Karyotype	CI-FISH	Therapy	Follow up (months)
1	11, M	152.8	Cortical T-ALL	n.a.	Split: MLLT10/10p12 Loss: PAX5, CDKN2A/B, Jak2/9p13-24 Gain: RP11-501C14/17q21.31	AIEOP LLA 2000	+73 alive [Brandimarte et al, 2013]
2	26, M	88	Cortical: CD45+, cyCD3+, TDT+, sCD3+, CD4+, CD5+, CD38+, CD1a+, CD34-, CD10-	46,Y,t(X;10)(p11;p12),add(1)(p36),del(9)(p11p24)[10]/ 46,idem,del(6)(q15)[1]/ 46,XY[11]	del(5q)/MAPK9,FLT4 del(6)(q15)/CASP8AP2 del(9)(p21)/CDKN2A/B	GIMEMA 0904 HLA identical SCT	+80 alive  [Brandimarte et al, 2014]
3	38, M	160	TDT+, CD7+, cyCD3+, CD5+, CD4+, CD8-	n.a.	del(9)(p21)/CDKN2A/B	GIMEMA 0904	Relapse +38 dead [Brandimarte et al, 2014]
4	31, M	700	n.a.	46,XY[20]	normal	GIMEMA 0904	Relapse +10 dead [Brandimarte et al, 2014]
5	16, M	68	CD45+, TDT+, HLA-DR+, CD7+, CD2+, sCD3+, CD5+, CD8+, CD19-, CD14-, CD13-, CD33-, CD34-, CD22-, CD20-, CD4-	46,XY[20]	del(9)(p21)/CDKN2A	GIMEMA 0496 unrelated SCT	Relapse +42 dead [Brandimarte et al, 2014]

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All patients achieved hematologic remission but 3 relapsed and died. Two patients are alive, one of them was treated by HLA identical Hematopoietic stem cell transplantation (HSCT).

DDX3X is one of the genes that escapes X-inactivation in females [Lahn B.T. et al., 1997]. As all patients with DDX3X-MLLT10 positive T-ALL were males, no wild-type DDX3X allele was retained in the leukemic blasts, suggesting that the complete absence of a normally functional DDX3X protein might contribute to leukemogenesis. DDX3X appeared to have oncogenic as well as tumor supressor functions [Change P.C. et al., 2006; Botlagunta M. et al., 2008; Brandimarte L., et al, 2014].

DDX3X/MLLT10