J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website http://www.thejh.org

Case Report

Volume 9, Number 1-2, April 2020, pages 23-29

Emergence of BCR-ABL1 Chronic Myeloid Leukemia in a JAK2-V617F Polycythemia Vera

**Table 1.** Clinical and Genetic Characteristics of Published Cases Including Initial Molecular Lesion *JAK2* in Combination With Molecular Change of *JAK2*, *BCR*/*ABL* or *JAK2* and *BCR*/*ABL*
Reference	Initial phenotype	Initial molecular lesion	Phenotype change	Molecular change	Observations
^aAdditional high WBC/thrombocytosis/erythrocytosis. ^bIn-frame deletion of six nucleotides (c.1620_1627delinsGA). PV: polycythemia vera; PMF: primary myelofibrosis; ET: essential thrombocytosis; CML: chronic myelogenous leukemia; TKI: tyrosine kinase inhibitor.
Siricilla et al, 2017 [10]	PV^a	JAK2	CML	Add BCR/ABL	Two clones by cytogenetics.
				Retain JAK2
Hummel et al, 2012 [6]	ET	JAK2	MF	Add BCR/ABL	BCR/ABL controlled with TKI.
				Retain JAK2
Zhou et al, 2015 [5]	PV	JAK2	CML	Add BCR/ABL	Two clones proved by progenitor colonies genotyping. Treatment: dasatinib and ruxolitinib.
				Retain JAK2
Swaminathan et al, 2018 [11]	PV	JAK2 exon12^b	CML	Add BCR/ABL (b3a3)	BCR/ABL controlled with TKI.
				Retain JAK2
Ursuleac et al, 2013 [12]	PV^a	JAK2	CML	Add BCR/ABL	BCR/ABL controlled with TKI.
				Retain JAK2
Jallades et al, 2008 [13]	PMF	JAK2	CML	Add BCR/ABL	BCR/ABL absent in first sample. BCR/ABL controlled with TKI. Persistent JAK2 with same ratio.
				Retain JAK2
Pingali et al, 2009 [14]	PV	JAK2	CML	BCR/ABL	PV-JAK2 re-emerge when BCR/ABL controlled.
Bocchia et al, 2007 [7]	PV	t(9;18)	CML	Add BCR/ABL	JAK2 positive tested in deferred in first sample.
				Retain t(9;18) JAK2
Yamada et al, 2014 [15]	PMF	JAK2	CML	Add BCR/ABL	BCR/ABL secondary event proved by progenitor colonies analysis.
Wang et al, 2015 [9]	PV	JAK2	CML	Add BCR/ABL	BCR/ABL secondary event on JAK2 cells proved by progenitor colonies genotyping.
	PV	JAK2	CML	Add BCR/ABL	BCR/ABL secondary event on JAK2 cells proved by progenitor colonies genotyping.
Mirza et al, 2007 [16]	PV	JAK2	CML	Add BCR/ABL	-
	PV	JAK2	CML	Add BCR/ABL	-
Hussein et al, 2008 [17]	PV	JAK2, BCR/ABL negative	CML	Add BCR/ABL	BCR/ABL controlled with TKI. Blast crisis of JAK2 clone.

Table 1. Clinical and Genetic Characteristics of Published Cases Including Initial Molecular Lesion JAK2 in Combination With Molecular Change of JAK2, BCR/ABL or JAK2 and BCR/ABL

Reference

Initial phenotype

Initial molecular lesion

Phenotype change

Molecular change

Observations

^aAdditional high WBC/thrombocytosis/erythrocytosis. ^bIn-frame deletion of six nucleotides (c.1620_1627delinsGA). PV: polycythemia vera; PMF: primary myelofibrosis; ET: essential thrombocytosis; CML: chronic myelogenous leukemia; TKI: tyrosine kinase inhibitor.

Siricilla et al, 2017 [10]

PV^a

JAK2

CML

Add BCR/ABL

Two clones by cytogenetics.

Retain JAK2

Hummel et al, 2012 [6]

JAK2

Add BCR/ABL

BCR/ABL controlled with TKI.

Retain JAK2

Zhou et al, 2015 [5]

JAK2

CML

Add BCR/ABL

Two clones proved by progenitor colonies genotyping. Treatment: dasatinib and ruxolitinib.

Retain JAK2

Swaminathan et al, 2018 [11]

JAK2 exon12^b

CML

Add BCR/ABL (b3a3)

BCR/ABL controlled with TKI.

Retain JAK2

Ursuleac et al, 2013 [12]

PV^a

JAK2

CML

Add BCR/ABL

BCR/ABL controlled with TKI.

Retain JAK2

Jallades et al, 2008 [13]

PMF

JAK2

CML

Add BCR/ABL

BCR/ABL absent in first sample. BCR/ABL controlled with TKI. Persistent JAK2 with same ratio.

Retain JAK2

Pingali et al, 2009 [14]

JAK2

CML

BCR/ABL

PV-JAK2 re-emerge when BCR/ABL controlled.

Bocchia et al, 2007 [7]

t(9;18)

CML

Add BCR/ABL

JAK2 positive tested in deferred in first sample.

Retain t(9;18) JAK2

Yamada et al, 2014 [15]

PMF

JAK2

CML

Add BCR/ABL

BCR/ABL secondary event proved by progenitor colonies analysis.

Wang et al, 2015 [9]

JAK2

CML

Add BCR/ABL

BCR/ABL secondary event on JAK2 cells proved by progenitor colonies genotyping.

JAK2

CML

Add BCR/ABL

BCR/ABL secondary event on JAK2 cells proved by progenitor colonies genotyping.

Mirza et al, 2007 [16]

JAK2

CML

Add BCR/ABL

JAK2

CML

Add BCR/ABL

Hussein et al, 2008 [17]

JAK2, BCR/ABL negative

CML

Add BCR/ABL

BCR/ABL controlled with TKI. Blast crisis of JAK2 clone.

**Table 2.** Clinical and Genetic Characteristics of Published Cases Including Initial Molecular Lesion *BCR*/*ABL* in Combination With Molecular Change of *JAK2*, *BCR*/*ABL* or *JAK2* and *BCR*/*ABL*
Reference	Initial phenotype	Initial molecular lesion	Phenotype change	Molecular change	Observations
^aAdditional high WBC/thrombocytosis/erythrocytosis. PV: polycythemia vera; MF: myelofibrosis; ET: essential thrombocytosis; CML: chronic myelogenous leukemia; TKI: tyrosine kinase inhibitor; AP: accelerated phase; Ph: Philadelphia positive chromosome.
Hummel et al, 2012 [6]	CML	BCR/ABL	MF	Add JAK2	BCR/ABL controlled with TKI. JAK2 low allele burden.
Darling et al, 2017 [18]	CML	BCR/ABL	ET	Add JAK2	BCR/ABL controlled with TKI.
Pagnanol et al, 2016 [19]	CML^a	BCR/ABL	ET	JAK2	BCR/ABL controlled with TKI.
Hussein et al, 2008 [17]	CML^a	BCR/ABL	MF	Add JAK2	-
	CML	Ph	MF	Add JAK2	BCR/ABL not evaluated.
Bader et al, 2019 [21]	CML^a	BCR/ABL	MF^a	JAK2	BCR/ABL controlled with TKI.
Curtin et al, 2005 [22]	ET	-	CML	BCR/ABL	Before JAK2 description, BCR/ABL positive in first sample.
Tefferi et al, 2010 [23]	CML	BCR/ABL	PV	Add JAK2	JAK2 positive when BCR/ABL controlled with TKI.
Kim et al, 2006 [20]	CML	BCR/ABL	MF	JAK2	JAK2 remain positive when BCR/ABL controlled with TKI.
	AP CML	BCR/ABL	-	JAK2	JAK2 remain positive when BCR/ABL controlled with TKI.

Table 2. Clinical and Genetic Characteristics of Published Cases Including Initial Molecular Lesion BCR/ABL in Combination With Molecular Change of JAK2, BCR/ABL or JAK2 and BCR/ABL

Reference

Initial phenotype

Initial molecular lesion

Phenotype change

Molecular change

Observations

^aAdditional high WBC/thrombocytosis/erythrocytosis. PV: polycythemia vera; MF: myelofibrosis; ET: essential thrombocytosis; CML: chronic myelogenous leukemia; TKI: tyrosine kinase inhibitor; AP: accelerated phase; Ph: Philadelphia positive chromosome.

Hummel et al, 2012 [6]

CML

BCR/ABL

Add JAK2

BCR/ABL controlled with TKI. JAK2 low allele burden.

Darling et al, 2017 [18]

CML

BCR/ABL

Add JAK2

BCR/ABL controlled with TKI.

Pagnanol et al, 2016 [19]

CML^a

BCR/ABL

JAK2

BCR/ABL controlled with TKI.

Hussein et al, 2008 [17]

CML^a

BCR/ABL

Add JAK2

CML

Add JAK2

BCR/ABL not evaluated.

Bader et al, 2019 [21]

CML^a

BCR/ABL

MF^a

JAK2

BCR/ABL controlled with TKI.

Curtin et al, 2005 [22]

CML

BCR/ABL

Before JAK2 description, BCR/ABL positive in first sample.

Tefferi et al, 2010 [23]

CML

BCR/ABL

Add JAK2

JAK2 positive when BCR/ABL controlled with TKI.

Kim et al, 2006 [20]

CML

BCR/ABL

JAK2

JAK2 remain positive when BCR/ABL controlled with TKI.

AP CML

BCR/ABL

JAK2

JAK2 remain positive when BCR/ABL controlled with TKI.

**Table 3.** Clinical and Genetic Characteristics of Published Cases Including Initial Molecular Lesion *JAK2* and *BCR*/*ABL* in Combination With Molecular Change of *JAK2*, *BCR*/*ABL* or *JAK2* and *BCR*/*ABL*
Reference	Initial phenotype	Initial molecular lesion	Phenotype change	Molecular change	Observations
^aAdditional high WBC/thrombocytosis/erythrocytosis. ^bBone marrow findings of other MPN. WBC: white blood cell; PV: polycythemia vera; PMF: primary myelofibrosis; ET: essential thrombocytosis; CML: chronic myelogenous leukemia; TKI: tyrosine kinase inhibitor; MPN: myeloproliferative neoplasm; MDS: myelodysplastic syndrome; CMR: Complete molecular response.
Bee et al, 2010 [24]	PV^a	JAK2 and BCR/ABL	CML	JAK2 present when BCR/ABL is treated, and vice versa.	Two clones with clonal dominance.
Payande et al, 2011 [25]	ET^a	JAK2 and BCR/ABL	No	No	-
Hummel et al, 2012 [6]	CML	JAK2 and BCR/ABL	PV	High JAK2 allele burden when PV phenotype.	PV phenotype when treated with imatinib.
Darling et al, 2017 [18]	Neutrophilic leukocytosis, basophilia and thrombocytosis	JAK2 and BCR/ABL	No	-	Treated with TKI.
Xu et al, 2014 [26]	CML	BCR/ABL and JAK2	No	-	Two clones? CMR with TKI, persistent JAK2.
Hassan et al, 2015 [27]	CML/MF	BCR/ABL and JAK2	No	-	JAK2 tested in deferred in first sample. Poor control of BCR/ABL with TKI.
Hussein et al, 2008 [17]	CML^b	BCR/ABL and JAK2	No	-	Concurrent lesions at the beginning.
Toogeh et al, 2011[28]	PV	JAK2 homozygous BCR/ABL	-	-	-
Park et al, 2013 [29]	ET	JAK2 and BCR/ABL	None	-	Poor response with hydroxyurea.
	PMF	JAK2 and BCR/ABL	-	-	BCR/ABL controlled with TKI.
Qin et al, 2014 [30]	ET	JAK2 and BCR/ABL	-	-	Diagnosis during pregnancy.
Kramer et al, 2007 [31]	CML	BCR/ABL	MF	JAK2	JAK2 positive tested in deferred in first sample.
Bornhauser et al, 2007 [8]	MF	-	-	BCR/ABL JAK2	BCR/ABL secondary event proved by progenitor colonies analysis.
Campiotti et al, 2009 [32]	CML	BCR/ABL and JAK2	-	-	JAK2 and BCR/ABL controlled with TKI.
Pastore et al, 2013 [33]	CML	BCR/ABL	TE	JAK2	JAK2 positive tested in deferred in first sample.
Cambier et al, 2008 [34]	PV	BCR/ABL and JAK2	-	-	Two clones proved by progenitor colonies analysis.
	CML
Conchon et al, 2008 [35]	MF	BCR/ABL and JAK2	-	-	JAK2 positive when BCR/ABL controlled with TKI.
	CML
Inami et al, 2007 [36]	CML^a	BCR/ABL	PV	JAK2	JAK2 positive tested in deferred in first sample.
Gattenlohner et al, 2009 [37]	CML	BCR/ABL	MDS/MPN	JAK2	JAK2 positive since the beginning.

Table 3. Clinical and Genetic Characteristics of Published Cases Including Initial Molecular Lesion JAK2 and BCR/ABL in Combination With Molecular Change of JAK2, BCR/ABL or JAK2 and BCR/ABL

Reference

Initial phenotype

Initial molecular lesion

Phenotype change

Molecular change

Observations

^aAdditional high WBC/thrombocytosis/erythrocytosis. ^bBone marrow findings of other MPN. WBC: white blood cell; PV: polycythemia vera; PMF: primary myelofibrosis; ET: essential thrombocytosis; CML: chronic myelogenous leukemia; TKI: tyrosine kinase inhibitor; MPN: myeloproliferative neoplasm; MDS: myelodysplastic syndrome; CMR: Complete molecular response.

Bee et al, 2010 [24]

PV^a

JAK2 and BCR/ABL

CML

JAK2 present when BCR/ABL is treated, and vice versa.

Two clones with clonal dominance.

Payande et al, 2011 [25]

ET^a

JAK2 and BCR/ABL

Hummel et al, 2012 [6]

CML

JAK2 and BCR/ABL

High JAK2 allele burden when PV phenotype.

PV phenotype when treated with imatinib.

Darling et al, 2017 [18]

Neutrophilic leukocytosis, basophilia and thrombocytosis

JAK2 and BCR/ABL

Treated with TKI.

Xu et al, 2014 [26]

CML

BCR/ABL and JAK2

Two clones? CMR with TKI, persistent JAK2.

Hassan et al, 2015 [27]

CML/MF

BCR/ABL and JAK2

JAK2 tested in deferred in first sample. Poor control of BCR/ABL with TKI.

Hussein et al, 2008 [17]

CML^b

BCR/ABL and JAK2

Concurrent lesions at the beginning.

Toogeh et al, 2011[28]

JAK2 homozygous BCR/ABL

Park et al, 2013 [29]

JAK2 and BCR/ABL

None

Poor response with hydroxyurea.

PMF

JAK2 and BCR/ABL

BCR/ABL controlled with TKI.

Qin et al, 2014 [30]

JAK2 and BCR/ABL

Diagnosis during pregnancy.

Kramer et al, 2007 [31]

CML

BCR/ABL

JAK2

JAK2 positive tested in deferred in first sample.

Bornhauser et al, 2007 [8]

BCR/ABL JAK2

BCR/ABL secondary event proved by progenitor colonies analysis.

Campiotti et al, 2009 [32]

CML

BCR/ABL and JAK2

JAK2 and BCR/ABL controlled with TKI.

Pastore et al, 2013 [33]

CML

BCR/ABL

JAK2

JAK2 positive tested in deferred in first sample.

Cambier et al, 2008 [34]

BCR/ABL and JAK2

Two clones proved by progenitor colonies analysis.

CML

Conchon et al, 2008 [35]

BCR/ABL and JAK2

JAK2 positive when BCR/ABL controlled with TKI.

CML

Inami et al, 2007 [36]

CML^a

BCR/ABL

JAK2

JAK2 positive tested in deferred in first sample.

Gattenlohner et al, 2009 [37]

CML

BCR/ABL

MDS/MPN

JAK2

JAK2 positive since the beginning.