Table 1 Comparison of JMML patients and... | American Society of Hematology

Table 1

Comparison of JMML patients and the Pten^fl/flNf1^+/− mouse model with previously reported mouse models

	JMML patients	Mx1-Cre
		Pten^fl/flNf1^+/−		Pten^fl/fl		Pten^fl/fl	Nf1^fl/fl or Nf1^-/fl	Lox-Stop-Lox (LSL)
		Pten^fl/flNf1^+/−		p55^−/−	p55^+/−	Pten^fl/fl	Nf1^fl/fl or Nf1^-/fl	Kras^G12D	Nras^G12D	Ptpn11^D61Y/+
Age mutation introduced	NApp	PND8	6 wk	PND2	6 wk	3 or 6 wk	PND3-PND5	3 wk	3 wk	3-4 wk
Age MPN occurs (postinduction)	2 y, often <1 y	3 wk (2 wk)	9 wk (3 wk)	T-ALL (7 wk)	T-ALL (3 wk)	7 wk (1-4 wk)	>3 mo (3 mo)	6 wk (3 wk)	>7 mo (6 mo)	5 mo (4 mo)
Survival	<1 y	3.5 wk*	11 wk	6-8 wk		7-12 wk	7.5 mo	>3 mo	>12 mo	>10 mo
Penetrance, %	NApp	100	100	100		90	100	100	100	100
Leukocytosis	Yes	Yes	Yes	Yes		Yes	No	Yes	Yes	Yes
Monocytosis	Yes	Yes	Yes	N/A		Yes	Yes	Yes	N/A	Yes
Lymphocytes	N/A	Decreased	Yes	Yes		N/A	Increased	N/A	Increased	N/A
Hemoglobin (hematocrit)	Decreased	Decreased	No	N/A		N/A	Normal	Decreased	Decreased	Decreased
Platelets counts	Normal/decreased	Elevated	No	N/A		N/A	Normal	Normal	Normal	Normal
Hypersensitivity to GM-CSF	Yes	No	N/A	N/A		N/A	Selective	Independent†	Independent†	Independent†
Hepatosplenomegaly	Yes	Yes	Yes	N/A		Yes	Yes	Yes	Yes	Yes
Cell infiltration in Lung	Yes	Yes	Yes‡	N/A		N/A	No	N/A	Yes§	No
AML or ALL	No (blasts <20%)	No	T-ALL	T-ALL		Yes	No	No	No	No
Other organs	Skin, lymph nodes, colon	Not found	Thymus, lymph nodes	Thymus, lymph nodes		Lymphoma	No	N/A	Lymph nodes, histiocytoma	No
Elevated Akt activity	55% patients	Constitutive	N/A	No	Yes	N/A	No	Yes	N/A	Yes
Elevated MAPK activity	73% patients	Yes‖	N/A	N/A		N/A	Yes‡	Yes	No	Yes
Reference	1, 22	The present study		33		29, 30	17	20, 21	19	18

	JMML patients	Mx1-Cre
		Pten^fl/flNf1^+/−		Pten^fl/fl		Pten^fl/fl	Nf1^fl/fl or Nf1^-/fl	Lox-Stop-Lox (LSL)
		Pten^fl/flNf1^+/−		p55^−/−	p55^+/−	Pten^fl/fl	Nf1^fl/fl or Nf1^-/fl	Kras^G12D	Nras^G12D	Ptpn11^D61Y/+
Age mutation introduced	NApp	PND8	6 wk	PND2	6 wk	3 or 6 wk	PND3-PND5	3 wk	3 wk	3-4 wk
Age MPN occurs (postinduction)	2 y, often <1 y	3 wk (2 wk)	9 wk (3 wk)	T-ALL (7 wk)	T-ALL (3 wk)	7 wk (1-4 wk)	>3 mo (3 mo)	6 wk (3 wk)	>7 mo (6 mo)	5 mo (4 mo)
Survival	<1 y	3.5 wk*	11 wk	6-8 wk		7-12 wk	7.5 mo	>3 mo	>12 mo	>10 mo
Penetrance, %	NApp	100	100	100		90	100	100	100	100
Leukocytosis	Yes	Yes	Yes	Yes		Yes	No	Yes	Yes	Yes
Monocytosis	Yes	Yes	Yes	N/A		Yes	Yes	Yes	N/A	Yes
Lymphocytes	N/A	Decreased	Yes	Yes		N/A	Increased	N/A	Increased	N/A
Hemoglobin (hematocrit)	Decreased	Decreased	No	N/A		N/A	Normal	Decreased	Decreased	Decreased
Platelets counts	Normal/decreased	Elevated	No	N/A		N/A	Normal	Normal	Normal	Normal
Hypersensitivity to GM-CSF	Yes	No	N/A	N/A		N/A	Selective	Independent†	Independent†	Independent†
Hepatosplenomegaly	Yes	Yes	Yes	N/A		Yes	Yes	Yes	Yes	Yes
Cell infiltration in Lung	Yes	Yes	Yes‡	N/A		N/A	No	N/A	Yes§	No
AML or ALL	No (blasts <20%)	No	T-ALL	T-ALL		Yes	No	No	No	No
Other organs	Skin, lymph nodes, colon	Not found	Thymus, lymph nodes	Thymus, lymph nodes		Lymphoma	No	N/A	Lymph nodes, histiocytoma	No
Elevated Akt activity	55% patients	Constitutive	N/A	No	Yes	N/A	No	Yes	N/A	Yes
Elevated MAPK activity	73% patients	Yes‖	N/A	N/A		N/A	Yes‡	Yes	No	Yes
Reference	1, 22	The present study		33		29, 30	17	20, 21	19	18

NApp, Not applicable; N/A, not available.

Equivalent to 1 to 3 y old in humans.

Colony growth in the absence of GM-CSF.

Only observed in Mac-1⁺ cells.

Lymphocytes.

Preference to GM-CSF over IL-3.