The diagnosis, prognosis, and therapeutic application of MicroRNAs in haematological malignancies

Figures & data

Table 1 Ectopic expression of miRNAs in AML concerning cytogenetic translocations and gene mutations

Alteration type	miRNAs expression differences	Clinical application	References
t(15,17)	Up-regulated: miR-127, miR-154, miR-154*, miR-299, miR-323, miR-368, miR-370, miR-224, miR-382, miR-134, miR-376a Down-regulated: miR-17-3p, miR-185, miR-187, miR-194, miR-200a, miR-200b, miR-200c, miR-330, miR-339	Patients with CN-AML and NPM1 mutations and no FLT3-ITD (NPM1 mutated/FLT3-ITD negative) are considered to comprise a molecular low-risk group that is similar to that of patients with core binding factor. AML: t (8;21) and inv (16). CEBPA	14,15,16
t(8;21)	Up-regulated: miR-126/126*, miR-146a Down-regulated: let-7b, let-7c, miR-133a, miR-223	mutations predicted better event-free, disease-free, and overall survival independently of other molecular and	14,15,16
inv(16)	Up-regulated: miR-126/126*, miR-99a, miR-100, miR-224 Down-regulated: let-7b, let-7c, miR-127	clinical prognosticators. Thus their related miRNAs also have significance in prognosis and may offer guidance regarding therapy.	14,15,16
KIT	Down-regulated: miR-29b		17
FLT3-ITD	Up-regulated: miR155, miR-10a, miR-10b, miR-511, miR-135a Down-regulated: miR-143, miR-338, miR-30a-3p, miR-182, miR-145, miR-130a, miR-214, miR-203		16,18,19,23
CEBPA	Up-regulated: miR-181family, miR-335, miR-128, miR-192, miR-219-1-3p, miR-224, miR-340 Down-regulated: miR-223, miR-196a, b, miR-149, miR-9, miR-21, miR-130b, let-7b, miR-194, miR-99b, miR-148a		16,20,21,22,24
NPMI mutation	Up-regulated: miR-10a, miR-10b, miR-196a, miR-196b, let-7, miR-29a, b, c, miR-16-1 Down-regulated: miR-204, miR-128a		16,18

Table 2 Ectopic expression of miRNAs in ALL

Items	MicroRNA	Expression in patients	Clinical significance	References
ALL compared to AML	miR-128a, b let-7b miR-223	Up-regulated Down-regulated Down-regulated	The specific miR expression of ALL can differentiate ALL from AML with a relative high accuracy.	25
CNS-relapsed ALL	miR-7 miR-198 miR-663 miR-126 miR-222 miR-551a miR-345	Up-regulated Up-regulated Up-regulated Down-regulated Down-regulated Down-regulated Down-regulated	To predict the occurrence of CNS relapse in ALL.	26
Paediatric ALL	miR-34a miR-128a miR-128b miR-146a	Up-regulated Up-regulated Up-regulated Up-regulated	Assist in diagnosing paediatric ALL.	26
ALL compared with normal CD34^+HPCs	miR-128a miR-142-3p miR-142-5p miR-150 miR-151-5p miR-181a, b, c miR-193a miR-30e-5p miR-34b miR-365 miR-582 miR-708 miR-100 miR-125b miR-99a miR-196b let-7e	Up-regulated Up-regulated Up-regulated Up-regulated Up-regulated Up-regulated Up-regulated Up-regulated Up-regulated Up-regulated Up-regulated Up-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated	May function as significant biomarkers in diagnosing ALL.	27
B-ALL T-ALL MLL	miR-708 miR-196b miR-196b	Up-regulated Up-regulated Up-regulated	Might be useful in differentiate B-ALL, T-ALL, and MLL.	27

Table 3 Ectopic expression of miRNAs in other types of leukaemia (CML and CLL)

Items	MicroRNA	Expression in patients	Clinical significance	References
Imatinib-resistant CML compared to Imatinib-responsive CML	miR-191 miR-7 miR-23a miR-26a miR-29a,c miR-30b,c miR-100 miR-126 miR-134 miR-141 miR-183 miR-196b miR-199a miR-224 miR-326 miR-422b miR-520a	Up-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated Down-regulated	To select proper patients before taking imatinib into clinical therapy.	34
CLL	miR-15a/miR-16-1 miR-155 miR-21 miR-34a	Down-regulated Up-regulated Up-regulated Down-regulated	These ectopic expressions are important molecular lesions and can be targets for therapy.	35,36,37,38,39
IgVH-mutated CLL	miR-150 miR-223 miR-29b, c	Up-regulated Up-regulated Up-regulated	Associated with biological features with known implications for prognostic factors and may prove to be useful in patient stratification.	38

Table 4 MiRNAs in relation to predicting prognosis of leukaemia

Related miRNAs	Changes	Clinical use	References
MiR-96	Down-regulated IN AML	Correlates with aggressive clinical features, worse RFS, and OS	40
miR-335	Up-regulated in AML	Correlates with aggressive clinical features	41
miR-124-1	Down-regulated in AML	Correlates with longer RFS and OS	42
miR-128b	Up-regulated in paediatric ALL	Correlates with better prognosis	43
miR-34a	Down-regulated in CLL	Correlates with poor prognosis	39
miR-328	Down-regulated in CML	Correlates with progression to the blast crisis phase of the disease	46
miR-18	Down-regulated during imatinib treatment	Correlates with early haematologic remission	47