Ultraconserved long non-coding RNA uc.112 is highly expressed in childhood T versus B-cell acute lymphoblastic leukemia

Chagas, Pablo Ferreira das; Sousa, Graziella Ribeiro de; Kodama, Márcio Hideki; Biagi Junior, Carlos Alberto Oliveira de; Yunes, José Andres; Brandalise, Silvia Regina; Calin, George Adrian; Tone, Luiz Gonzaga; Scrideli, Carlos Alberto; Oliveira, Jaqueline Carvalho de

doi:10.1016/j.htct.2019.12.003

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Hematology, Transfusion and Cell Therapy

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Original Articles • Hematol., Transfus. Cell Ther. 43 (1) • Jan-Mar 2021 • https://doi.org/10.1016/j.htct.2019.12.003 copy

Ultraconserved long non-coding RNA uc.112 is highly expressed in childhood T versus B-cell acute lymphoblastic leukemia

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Aberrant expression of long non-coding RNAs (lncRNAs) has been detected in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped on transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated by quantitative real-time PCR in bone marrow samples from children with T-ALL (n = 32) and common-ALL/pre-B ALL (n = 30). In pediatric ALL, higher expression levels of uc.112 were found in patients with T-ALL, compared to patients with B-ALL. T-cells did not differ significantly from B-cells regarding uc.112 expression in non-tumor precursors from public data. Additionally, among B-ALL patients, uc.112 was also found to be increased in patients with hyperdiploidy, compared to other karyotype results. The uc.122, uc.160, and uc.262 were not associated with biological or clinical features. These findings suggest a potential role of uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.

Keywords:
Pediatric acute lymphoblastic leucemia; uc.112; T-ALL; Hyperdiploidy

Gene expression	Event-free survival				Overall survival
Gene expression	Cumulative survival ± SD (%)	p-Value^a a Log-rank test.	HR (95 % CI)	p-Value^b b Univariate Cox regression.	Cumulative survival ± SD (%)	p-Value^a a Log-rank test.	HR	95% CI	p-Value^b b Univariate Cox regression.
uc.112
< median	61.6 ± 9.9	0.49	0.71 (0.27-1.87)	0.49	67.7 ± 12.3	0.84	0.89	0.30-2.66	0.84
> median	73.5 ± 0.86				77.4 ± 8.1
uc.122
< median	71.6 ± 8.6	0.66	1.24 (0.48-3.21)	0.66	82.9 ± 7.0	0.37	1.66	0.54-5.09	0.37
> median	63.2 ± 9.9				63.3 ± 11.5
uc.160
< median	56.5 ± 9.7	0.2	0.51 (0.18-1.45)	0.20	63.4 ± 13.3	0.64	0.77	0.25-2.35	0.65
> median	76.9 ± 9.1				76.7 ± 9.1
uc.262
< median	65.7 ± 10.8	0.91	0.94 (0.32-2.80)	0.91	77.1 ± 9.0	0.87	1.11	0.32-3.84	0.87
> median	68.0 ± 10.9				52.9 ± 22.5

	Event-free survival			Overall survival
	HR	95% CI	p-Value	HR	95% CI	p-Value
Age	8.80	1.80-42.93	0.007	15.01	1.79-126.12	0.01

WBC	7.87	1.40-44.06	0.02	6.05	0.82-44.44	0.08

Hyperd	11.48	0.98-134.90	0.052	23.55	1.41-392.55	0.03

uc.112	0.24	0.02-3.51	0.3	0.45	0.03-6.56	0.56

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

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[1] *Corresponding author at: Department of Genetics, Federal University of Parana, Rua Evaristo F. F. da Costa, 418, CEP: 80050-540, Curitiba, PR, Brazil. E-mail address: jaqueline.carvalho@ufpr.br (J.C. de Oliveira).

T-UCR	Age		p-Value
T-UCR	1 to 9 years (n = 34)	<1 and >9 years (n = 25)	p-Value
uc.112	0.56 (0.05-25.19)	0.90 (0.03-3.24)	0.93
uc.122	2.29 (0.51-10.28)	1.75 (0.6-10.92)	0.17
uc.160	3.16 (0.79-26.71)	2.86 (0.31-32.11)	0.47
uc.262	0.64 (0.11-3.05)	0.57 (0.07-2.03)	0.82
T-UCR	WBC at diagnosis		p-Value
T-UCR	≤50,000/mm³ (n = 26)	>50,000 mm³ (n = 33)	p-Value
uc.112	0.82 (0.03-25.19)	0.53 (0.05-10.37)	0.90
uc.122	1.8 (0.51-10.92)	2.19 (0.7-7.49)	0.66
uc.160	4.03 (0.79-32.11)	2.56 (0.31-14.07)	0.11
uc.262	0.64 (0.07-2.61)	0.53 (0.11-3.05)	1.00
T-UCR	Immunophenotype		p-Value
T-UCR	B-ALL (n = 30)	T-ALL (n = 32)	p-Value
uc.112	0.43 (0.05-1.46)	1.10 (0.03-25.19)	0.003
uc.122	1.76 (0.51-4.02)	2.19 (0.29-10.92)	0.08
uc.160	2.48 (0.79-11.41)	4.03 (0.31-32.11)	0.12
uc.262	0.67 (0.11-3.05)	0.36 (0.07-32.11)	0.44
T-UCR	Hyperdiploid		p-Value
T-UCR	Presence (n = 9)	Absence (n = 21)	p-Value
uc.112	0.95 (0.70-1.46)	0.30 (0.05-1.06)	<0.001
uc.122	2.12 (1.46-3.32)	1.61 (0.6-4.02)	0.47
uc.160	4.69 (2.09-11.41)	1.73 (0.92-7.28)	0.12
uc.262	0.8 (0.33-0.8)	0.53 (0.14-3.05)	0.25
T-UCR	t(12;21)		p-Value
T-UCR	Presence (n = 7)	Absence (n = 23)	p-Value
uc.112	0.26 (0.06-1.06)	0.51 (0.05-1.46)	0.24
uc.122	1.15 (0.51-2.46)	2.12 (0.6-4.02)	0.23
uc.160	1.71 (0.79-7.2)	2.73 (0.92-11.41)	0.48
uc.262	0.67 (0.49-2.61)	0.69 (0.11-3.05)	0.45