. 2021 Jun 23;13:4987–5000. doi: 10.2147/CMAR.S314343

Table 1.

Genetic, Chromosomal, Telomere Biology and Epigenetic Modification Changes Associated with BP Transformation

	Candidates	Alterations	Features	Functions and Mechanisms
	BCR-ABL kinase domain²⁸^,^30–32	Mutation	Y253F E255K	Increases carcinogenic potency, enhances autophosphorylation and tyrosine phosphorylation
	BCR-ABL kinase domain²⁸^,^30–32	Mutation	T315I	Decreases sensitivity to imatinib
	p53³⁴^,³⁶	Loss	—	Apoptosis disorder Cannot eliminate genetically defective cells
	IKZF1³⁷	Deletion	—	Affects pre–B cell differentiation
	MYC^38–40	Upregulation	—	Mitochondrial genome instability, blocks cell growth, upregulates BCR-ABL expression, suppresses miR-150, decreases sensitivity to imatinib
Genetic Events	RUNX1⁴⁴	Mutation	H78Q, D171G, R174Q, R139G, G381fster570, R174Q, V91fs-ter94	Induces BCR-ABL-expressing mice to develop mortal CML-BP-like or CML-AP-like diseases
	GATA-2⁴⁶	Mutation	—	Interferes with the myelomonocytic differentiation of BCR-ABL-expressing BM hematopoietic stem/progenitor cells
	UBE2A⁹	Mutation	—	Abrogates myeloid cell differentiation
	PP2A⁵¹	Inactivation	—	Restoration of PP2A activity reduces the leukemic potential of BCR-ABL in vitro
	β-Catenin pathway⁵⁰^,⁵⁴	Activation	—	Enhances cell self-renewal ability Promotes DNMT1 transcription, silencing PTPRG by the hypermethylation of its promoter region
	CBL, CBLB, IDH1/2, ASXL1, TET2⁵⁵	—	—	Accessory karyotypic abnormalities in advance CML
	CEBPA⁵²^,⁵³	Inactivation	—	Abrogates myeloid cell differentiation
	SOCS2, CD52	Upregulation	—	Higher frequency in the BP population
	MPO, PRAME, HLA antigens, JunB, Fos and FosB⁸	Downregulation	—	Higher frequency in the BP population
ACAs⁵⁶^,⁵⁸	—	Numeric Changes	+8, +21, i (17q), 3q26.2 rearrangement, +Ph, −7/7q-, +19	Higher frequency in the BP population
ACAs⁵⁶^,⁵⁸	—	Structural changes	t (1;21); t (3;21); t (7;11)	Higher frequency in the BP population; formation of the fusion protein
Telomere Biology⁵⁹^,⁶⁰^,⁶²	Telomere length	Shortening	—	Higher frequency and telomere length are shorter in the BP population, accelerated telomere shortening conferring cells growth advantages
Telomere Biology⁵⁹^,⁶⁰^,⁶²	Telomerase activity	Decreasing	—	Induces BCR-ABL-expressing cells expansion limited and stop proliferating, with morphological characteristics of apoptosis death in vitro
Epigenetic Modification^63–66	Methylated CpG	Upregulation	HIC1, MEG3 promoter, miR-147 promoter	Higher frequency in the BP population and mediates CML blast crisis transformation
	Methylated CpG	Downregulation	EPB41L3, PRDX2, PLCL1, TUSC1, BCL11B, NDRG2
	Histone modification	Increased	RBP2

Notes: This table represents the molecular mechanisms involved in CML progression.

Abbreviations: CML, chronic myeloid leukemia; AP, accelerated phase; BP blast phase; BM, bone marrow.