Table 1. MiRNA involvement in hematological malignancies.

miRNA	Hematopoiesis	Ref	Development and progression of cancer	Suggested mechanism in hematological cancers	Ref	Response to treatment	Ref	Possible protein targets*
miR-15 miR-16	miR-16: regulates differentiation of late erythroid progenitor cells	[159]	Tumor-suppressor in CLL Possibly different roles in early and late-stage MM	Cell cycle arrest Decrease in proliferation Antiangiogenic activity	[7, 81, 91-93]	MiR-15a expression increased in MM cell lines in the presence of bortezomib, decreased when BMSC were added	[92]	Bcl2, cyclin D1, cyclin D2, CDC25A, pRb, AKT3, pAKT, rpS6, pERK, TAB3, VEGF miR-16: RARS
miR-17-92 cluster	Essential for Pro-B and Pre-B-cell survival	[74]	Oncogene in B-cell lymphoma miR-17: Tumor-suppressor in miR-92a-induced erythroleukemia	Decrease in apoptosis (possibly due to elevated myc) Increases cell proliferation Promotes cell survival Promotes the development of stem cell properties or characteristics of early developmental lineages Activation of the PI3K/AKT pathway	[103, 111, 113, 128, 160, 161]	Overexpression increased survival of MCL cell lines after treatment with topotecan, doxorubicin, or etoposide Downregulation suppressed tumor growth in a mouse model of MCL treated with doxorubicin miR-19a and miR-19b were downregulated in MM cell lines in the presence of ITF2357 miR-17: High expression associated with shorter OS in MM patients	[128, 129, 142]	p53, Gata-1, PTEN, E2F1, Bim, PHLPP2 miR-17: Bcl2, STAT-5, Jak2, p21 miR-19a and miR-19b: SOCS1 miR-92: KLF2 [63]
miR-21	---	---	Oncogene in MM and B and T-cell lymphoma	Decrease in apoptosis	[13, 99-104, 162]	Associated with resistance to CHOP in DLBCL	[130]	PTEN, PPCD4, Bim, SHIP1
miR-27a	Promotes erythroid differentiation	[163]	---	---	---	Lower expression in K562 cells resistant to doxorubicin	[134]	MDR1, STAT-5, GATA2 [159]
miR-28	Involved in the GC reaction	[114]	Tumor-suppressor in GC-derived lymphomas	Decrease in proliferation and clonogenicity Increase in apoptosis	[114]	---	---	BAG1, MAD2L1, RAP1B
miR-34a	Delays Pro-B to Pre-B-cell transition Essential for transdifferentiation from Pre-B-cells to macrophages	[164, 165]	---	---	---	In the presence of bortezomib, downregulation of miR-34a increased apoptosis of P493-6 cells miR-34a overexpression in TP53-mutated MM cell lines and mice inhibited tumor growth	[125, 127]	Myc, p53, BCL2, CDK6, NOTCH1, Lef1, Foxp1
miR-122	---	---	---	---	---	Protective action against treatment with bortezomib, MG132, and GSI-1	[139]	cyclin G1
miR-127-3p	---	---	---	---	---	Prognostic role in MCL patients especially in combination with other clinical indicators	[141]	BLIMP1
miR-146b-5p	---	---	Tumor-suppressor in DLBCL	Decrease in proliferation	[143]	Lower expression in CHOP-treated DLBCL patients with poorer OS	[143]	---
miR-150	Blocks Pro-B to Pre-B-cell transition High expression in T-cells Downregulation during erythroid and megakaryocytic differentiation	[64, 66, 159]	Tumor-suppressor in NK/T-cell lymphoma	Increase in apoptosis (especially in the presence of inhibition of miR-21) Decrease in cell proliferation Control of aging and senescence by decreasing telomerase activity	[2]	---	---	DKC1, AKT2, Myb, Survivin, Foxp1, cMYB
miR-155	Controls GC reaction Regulates T helper cell differentiation	[69]	Oncogene in B-cell lymphoma	Decrease in apoptosis	[109, 162]	---	---	PTEN, PPCD4, Bim, SHIP1, FXR1, Ago2, c-Maf, Pu.1, AID, CXCR4, JUN, GATA-3 [159]
miR-181a/b	Early differentiation of B-cells Decrease in proliferation of T-cells Decrease granulocytic and macrophage-like differentiation	[62, 147, 164, 166]	Oncogenes in NHL and AML	NHL: Decrease in apoptosis AML: blockage of myeloid differentiation and infiltration of leukemic cells into the bone marrow and spleen	[144, 145, 147, 148]	Promote apoptosis in fludarabine-exposed CLL cells that express p53 Prognostic potential in CLL showing downregulation during progressive disease	[144, 145]	CXCR4 [63], BCL2, MCL1, TCL1, XIAP, PRKCD miR-181a: Bim, CAMKK1, CTDSPL miR-181b: AID
miR-221 miR-222	Downregulation is essential for expansion of erythroblasts	[115, 159]	Oncogenes in MM	Increase of DNA replication AKT activation	[115, 116, 159]	---	---	p27Kip1, PTEN, p57Kip2, c-kit
miR-223	Involved in the transition from GC cells to post-GC cells Controls granulocytic differentiation Essential for transdifferentiation from Pre-B-cells to macrophages	[36, 63, 165, 167]	---	---	---	---	---	NFI-A, Lef1
miR-320d	---	---	Tumor-suppressor in DLBCL	Decrease in proliferation	[143]	Lower expression in CHOP-treated DLBCL patients with poorer PFS and OS	[143]	---
miR-331-5p	---	---	---	---	---	Lower expression in K562 cells resistant to doxorubicin	[134]	MDR1
miR-615-3p	---	---	---	---	---	Prognostic role in MCL patients especially in combination with other clinical indicators	[141]	---
miR-886-5p	---	---	---	---	---	High expression associated with shorter OS in MM patients	[142]	NR3C1

^*Based on references mentioned for Hematopoiesis, Development and progression of cancer, and Response to treatment, unless otherwise stated.

Ago2: Argonaute-2; AID: Activation-induced cytidine deaminase; AKT3: AKT serine/threonine protein kinase-3; BAG1: Bcl2-associated athanogene; DKC1: Dyskerin; FKBP51: FK506-binding protein 51; FXR1: Fragile-X mental retardationrelated protein 1; MAD2L1: MAD2 mitotic arrest deficient-like 1; PDCD4: Programmed cell death 4; PHLPP2: PH domain and Leucine-rich repeat Protein Phosphatase 2; PTEN: Phosphatase and tensin homologue; RAP1B: member of RAS oncogene family; RARS: Arginyl-tRNA synthetase gene; rpS6: ribosomal-protein-S6; SHIP1: Src homology-2 domain-containing inositol 5-phosphatase 1; SOCS1: Suppressor of cytokine signaling 1; TAB3: TGF-beta activated kinase 1/MAP3K7 binding protein 3; VEGF: Vascular endothelial growth factor; XIAP: X-linked inhibitor of apoptosis protein.