Treating hematological malignancies with drugs inhibiting ribosome biogenesis: when and why

Table 2 Overview of genomic alterations involved in the regulation of the RP/MDM2/p53 axis in hematologic malignancies

Genomic alteration	Disease type	Incidence of the alteration	Prognostic impact	Proposed Mechanism	Reference
TP53 mutation	DLBCL	22%-24%	Poor	Impaired p53 mediated response to nucleolar stress	[14, 146]
	CLL	7-9%	Poor		[94, 147–149]
	ALCL	8%	Poor		[145]
	ALL	14-15%	Poor		[15, 150]
	AML	5%-9%	Poor		[92, 151]
	MM	<5%	Poor		[152]
TP53 deletion	DLBCL	12%	Poor		[16]
	CLL	5-12%	Poor		[147, 148]
	ALL	11%	Poor		[15]
	MM	9.5%	Poor		[152]
ARF deletion	DLBCL	35%	Poor	Increased MDM2-dependent p53 degradation	[153]
	FL	8%	Poor		[154]
	ALL	14-15%	Poor		[15, 150, 155]
RB1 loss	DLBCL	11%	Neutral	Loss of G1/S checkpoint	[156]
	CLL	20%	Neutral		[157]
	ALCL	40%	Good		[103]
	ALL	9%	Neutral		[158, 159]
RPS15 mutation	CLL	19% (RELAPSE)	Poor	Impaired p53 mediated response to nucleolar stress	[118]
RPL5 mutation	MM	Sporadic	NE		[111]
RPL5 mutation	T-ALL	<5%	NE		[108]
RPL5 deletion	MM	20%	Poor		[110]
RPL10 mutation	T-ALL	5%	NE		[108]
RPL22 deletion	T-ALL	10%	NE		[160]
NPM1 mutation	AML	53%	Good*	Increased sensitivity to nucleolar stress	[91]
NPM1-ALK	ALCL	55%	Good	Increased sensitivity to nucleolar stress	[161]

Abbreviations: NE (not evaluated), DLBCL (diffuse large B-cell lymphoma), FL (Follicular lymphoma), CLL (chronic lymphoid leukemia), ALCL (anaplastic large T-cell lymphoma), ALL (acute lymphoid leukemia), T-ALL (T-cell acute lymphoid leukemia), MM (Multiple Myeloma), AML (acute myeloid leukemia)
*Associated with good prognosis in the absence of FLT3 genomic alterations

ISSN: 1756-8722