Table 2. Cytogenetics, Hematologic and Clinical Characteristics and Treatment Outcome of Patients with Reciprocal Translocations Hitherto Not Reported in AML or MDS^a.

Case no.	Age/Sex	Race	Karyotype	FAB	AML/MDS Type	Hb (g/ dL)	Plts (×109/L)	WBC (×109/L)	PB/BM blasts (%)	Auer rods (+/−)	Organ Involvement	Responseb	DFS (mo)	OS (mo)	Induction Rxc	Post-CR Rxc
Common breakpoint: 3p25
11	56/F	White	46,XX,t(1;3)(p32;p25)[37]	M4	de novo	5	153	23.8	50/72	-	No	CR	35.4	66.7+	ADx2 8525	HIDAC 8525
A similar translocation, described as t(1;3)(p32;p26), has been reported in a patient with ALL (Nagasaka et al., 1983). The constitutional nature of this abnormality could not be excluded.
12	56/M	White	46,XY,t(3;4)(p25;p16)[4]/46,XY[18]	M0	de novo	8.1	384	2.9	1/47	-	No	R	NA	1.3	ADE 19808	NA
Common breakpoint: 4q24
13	39/M	White	46,XY,t(4;12)(q24;q12)[16]/46,XY[4]	M4	de novo	11.3	184	3.1	41/22	-	No	CR	37.4	38.8	ADE 10503	AlloSCT
14	27/M	White	46,XY,t(4;21)(q24;q22)[2]/46,XY[18]	M1	de novo	9.5	17	114.2	88/90	-	No	DA	NA	1.3	ADEx2 10503	NA
Common breakpoint: 6p21
15	84/M	White	46,XY,t(1;6)(p33;p21)[38]/46,XY[14]	UAL	t-AML	12.5	27	140	84/86	-	H	R	NA	0.6	A/L 8721	NA
16	55/M	White	47,XY,+21[6]/47,idem,t(6;8)(p21;q24)[5]/46,XY[9]	M1	de novo	7.9	86	2.8	17/83	-	LAD	R	NA	15.6+	CY/D/V/P/L 9311	NA
A similar translocation, described as t(6;8)(p12;q24), has been reported in accelerated phase CML (Offit et al., 1990).
Common breakpoint: 8p21
17	37/F	White	46,XX,t(1;8)(q32;p21),t(11;14) (p15;q24)[16]/46,XX[3]	NA	RD	11.4	99	3.3	7/62	-	H	R	NA	10.3	DEC/VA	NA
The t(1;8) was acquired at the time of relapse. At diagnosis, the patient had de novo AML and a normal karyotype.
18	60/M	White	47,XY,t(8;12)(p21;q24.1),+10[7]/46,XY[13]	NA	RD	13.8	184	3.2	0/25	NR	NR	NR	NA	46+	AlloSCT	NA
The t(8;12) was acquired at the time of relapse. At diagnosis, the patient had de novo AML and a normal karyotype.
Common breakpoint: 8q13
19	75/M	White	47,XY,t(5;8)(p13;q13),+10[15]/46,XY[5]	RA	de novo	10.4	72	2.7	0/2	NA	No	R	NA	9.7	Vatalanib ×2 10105	NA
20	57/F	White	46,XX,t(8;11;18)(q13;p13;q21.1)[6]/46,XX[16]	M1	de novo	9.1	28	0.7	8/62	NR	No	CR	11.8	19.5	ADE 10503	B/E, AutoSCT 10503
t(8;11;18)(q13;p13;q21.1) may represent a three-way variant of t(8;18), t(8;11) or t(11;18). The t(8;18)(q13;q21) has been reported in one case of AML-M5b (Yamamoto et al., 2007) and a t(8;11)(q13;p14) with similar, but not identical, breakpoints in one case of AML-M5a with concurrent t(9;11)(p22;q23) (Swansbury et al., 1998). No t(11;18) with similar breakpoints has been published (Mitelman et al., 2012).
Common breakpoint: 8q22
21	33/F	White	46,XX,t(3;17;8)(p21;q25;q22)[16]/46,XX[4]	M2	de novo	9.6	64	9.2	22/41	+	No	CR	169.7+	170.4+	AD 9222	HIDAC/ CY/E/AZ/MX 9222
t(3;17;8)(p21;q25;q22) may represent a three-way variant of t(8;17), t(3;17) or t(3;8). The t(8;17)(q22;q25) has been reported in one case of pediatric AML (Raimondi et al., 1999) and one case of CML in accelerated phase (Mashal et al., 1990). t(3;17)(p21;q25) has been reported in one case of CML in blastic phase (Sessarego et al 1987) and one case of pediatric ALL (Raimondi et al., 1992). No t(3;8) with similar breakpoints has been published (Mitelman et al., 2012).
22	58/F	White	46,XX,t(8;12)(q22;p11.2),t(8;14) (q24.1;q32)[17]/46,XX[8]	NA	RD	13.4	64	2.2	NR/26	NR	NR	R	NA	15.4	FLAG-I/MY	NA
The t(8;12) was acquired at the time of relapse. At diagnosis, the patient had de novo AML and a normal karyotype. Similar translocations, described as t(8;12)(q22;p12) (Mrózek et al., 2002) and t(8;12)(q22;p11-12) (Olopade et al., 1992) each being part of complex karyotypes, have been reported in patients with AML-M2 and AML-M6, respectively. This patient is also included in Table 1 (case 9) because she also harbors t(8;14)(q24.1;q32).
23	28/F	White	46,XX,t(8;20)(q22;p13)[12]/46,XX[8]	M4	de novo	11.9	33	11.6	29/56	+	LAD	CR	134.1+	135.5+	ADx2 8221	A 8221
Cases with an identical translocation have been reported; however both were shown to be variants of t(8;21) with RUNX1/RUNX1T1 gene fusion (Taviaux et al., 1999; Xue et al., 1997).
Common breakpoint: 11p15
24	44/M	White	46,XY,t(3;11)(p23;p15),del(16)(q22)[40]	M4	de novo	10.1	80	78.6	40/41	NR	No	CR	18.2	40.6	AI 9120	NR
A similar translocation, described as t(3;11)(p24;p15), has been reported in a patient with AML-M5a (Nebral et al., 2005). Karyotypically normal cells were detected in the patient's sample at the time of relapse.
25	19/M	White	46,XY,t(3;11)(p11;p15)[31]	M4	de novo	10	79	108	40/56	+	No	CR	92+	92.9+	AD 9022	HIDAC/CY/E 9022
A similar translocation, described as t(3;11)(p12;p15), has been reported in a patient with T-ALL (Cauwelier et al., 2006). The acquired, non-constitutional nature of the translocation has been confirmed by a cytogenetically normal result of phytohemagglutinin-stimulated blood analysis.
Common breakpoint: 13q14
26	32/F	White	47,XX,t(2;13)(p23;q14),+21[4]/46,XX[55]	M2	de novo	8.4	41	8.3	56/52	+	No	CR	13.9	16.1+	AD 8821	CY/E 8821
A similar translocation, described as t(2;13)(p21;q12), has been reported in a patient diagnosed with RAEB (Kiuru-Kuhlefelt et al., 1997), and t(2;13)(p21;q14.11) has been detected in a patient with AML-M6a (Poitras et al., 2011).
27	41/M	White	47,XY,t(5;13)(q15;q14),+mar[22]	M4	de novo	8.3	29	68	57/31	-	No	R	NA	4.3	ADEP 9621	NA
Karyotypically normal cells were detected in follow-up samples.
Common breakpoint: 14q32
28	54/M	White	46,XY,t(3;14)(q25;q32)[36]/46,XY[4]	AML NOS	de novo	9.6	282	40.4	92/NR	NR	No	R	NA	11.3	ADx2 8525	NA
A similar translocation, described as t(3;14)(q24;q32), has been reported in one ALL patient (Kristensen et al., 2003).
29	55/M	White	46,XY,t(8;14)(q11.2;q32)[8]/46,XY[12]	M0	de novo	7.8	63	56.2	53/69	-	No	R	NA	4.1	ADE 9621	NA
t(8;14)(q11;q32) is a recurrent translocation in ALL (Mitelman et al., 2012), but hitherto has not been reported in AML. It has been reported as part of a complex karyotype detected in a patient with CML (Hu et al., 1990).
Common breakpoint: 15q15
30	33/F	White	46,XX,t(2;15)(p11;q15) or t(2;15)(p1?3;q22)[2]/46,XX[17]	M2	de novo	7.7	334	1.5	4/40	-	Skin/ LAD	CR	9	38	ADx2 8821	MX/AZ 8821
A translocation interpreted as t(2;15)(p1?3;q2?2) has been reported in a patient with AML-M4 (Steudel et al., 2003).
31	55/M	White	46,XY,t(3;15)(p21;q15)[4]/45,XY,−20[3]/46,XY[12]	M4	de novo	10.4	59.0	40.1	54/71	+	No	CR	4.4	9.3	AD 8525	IDAC 8525
The t(3;15)(p21;q15) has also been reported to be acquired during blast crisis in a patient with CML (Anastasi et al., 1996) and in a patient with a chronic myeloproliferative disorder (Shearer et al., 2010). Additionally, t(3;15)(p21;q15) was detected in two pediatric patients with ALL, as a sole abnormality in one case and in addition to t(9;22)(q34;q11) in another (Heerema et al., 2002).
32	59/M	White	46,XY,t(7;15)(q32;q15),del(16) (q13q24)[8]/46,XY[17]	NA	RD	11	216	1.6	1/38	-	NR	R	NA	13.6	A	NA
The t(7;15) was acquired at the time of relapse. At diagnosis, the patient had de novo AML and the following karyotype: 91,XXYY,−3[3]/46,XY[17].
33	39/M	White	46,XY,t(11;15)(p15;q15)[19]/46,XY[1]	M3	NR	10.5	52	7.5	55/89	+	NR	CR	69.7+	70.6+	AD/ATRA 9710	Arsenic, ATRA/D 9710
This patient had a submicroscopic rearrangement, an insertion of PML into the RARA gene resulting in PML-RARA gene fusion, which was confirmed using RT-PCR. Thus, the t(11;15) is likely an aberration secondary to the PML-RARA fusion. To our knowledge, there are no reported cases involving NUP98 as a secondary aberration in APL. There is a reported case of AML-M4 with a similar translocation, t(11;15)(p15;q14) (Milton et al., 1984).
34	75/M	White	46,XY,t(15;15)(q15;q26)[23]/46,XY[4]	M2	t-AML	8.6	135	2.5	4/40	-	No	CR	5.7	20.9+	ADE 9720	ADE 9720
A similar translocation, described as t(15;15)(q14;q26), has been reported in a patient with therapy-related AML (Olney et al., 2002).
Common breakpoint: 17q11.2
35	36/F	U	46,XX,t(10;17)(p13;q11.2),add(13) (q34)[18]	M0	de novo	10	32	4.4	34/77	-	No	CR	47.6+	49.9+	ADEx2 10503	A/AlloSCT reduced intensity
Similar translocations, t(10;17)(p13;q12) and t(10;17)(p13;q12-21), have been described in two patients with AML-M0 (Laï et al., 1989), and t(10;17)(p13-15;q12-21) was found in AML-M1 (Oh et al., 2010). Only karyotypically normal cells were detected in a CR sample.
36	38/M	Black	46,XY,t(16;17)(q22;q11.2)[13]/46,XY[7]	M6	de novo	7	54	5.7	50/29	+	No	R	NA	15.4+	ADx2 9022	NA
This case was previously reported as part of a series of patients with AML M6 (Davey et al., 1995).
Common breakpoint: 17q21
37	48/M	White	46,XY,t(3;17)(q24;q21)[25]	M2	de novo	4.9	22	7.5	51/68	-	No	R	NA	16.6+	ADx2 8525	NA
Karyotypically normal cells were detected in follow-up samples.
38	52/F	White	46,XX,add(7)(q21),t(7;17)(p21;q21)[21]	M2	de novo	9.2	101	21.9	8/33	-	H/S	CR	3.7	8.5	ADE 19808	HIDAC/E 19808
A similar translocation, described as t(7;17)(p22;q22), has been reported in a patient with T-ALL (Karst et al., 2006). Only karyotypically normal cells were detected in a CR sample, and there were karyotypically normal cells in the patient's sample at the time of relapse.
39	63/M	White	46,XY,t(11;20;17)(q13;q13.1;q21) [10]/45,idem,-Y[12]/46,XY[3]	M5a	de novo	9	94	50.1	69/99	-	No	CR	2.7	5.2	ADE 9720	ADE 9720
t(11;20;17)(q13;q13.1;q21) may represent a three-way variant of t(11;20), t(20;17) or t(11;17). The t(11;17)(q13;q21) has been reported in a patient with AML-M2 (Yasar et al., 2010) and as a rare variant translocation in AML-M3 (Wells et al., 1996).
Other breakpoints
40	18/M	White	46,Y,t(X;8)(p11.2;q11.2),t(11;13) (q12;q12)[9]/46,XY[24]	M1	de novo	8.4	70	60.4	92/96	+	Gums	R	NA	3.4	ADx2 8525	NA
41	48/F	White	46,X,t(X;10;10)(p11.2;p11.2;q13), del(12)(p12p13)[14]/46,XX[6]	M0	de novo	12.6	138	21.3	71/84	-	No	CR	10.3	13.6	ADE 10503	HIDAC
This case may represent a variant of a rare recurrent abnormality in AML t(X;10)(p11.2;p11.2) (Mitelman et al., 2012).
42	55/M	White	46,Y,t(X;12)(q2?4;q1?5)[6]	M2	de novo	8.5	38	6.2	33/38	+	No	CR	23.8	78.7+	ADE 19808	HIDAC/E 19808
A similar translocation, described as t(X;12)(q24;q13), has been reported in one AML patient (Kerndrup & Kjeldsen, 2001). Karyotypically normal cells detected in the patient's sample at the time of relapse.
43	44/F	White	46,XX,t(1;4)(q42;q21)[16]/46,XX[4]	M2	NR	10	67	110.8	85/61	+	No	CR	7.4	83.6	ADE 19808	B/E, AutoSCT 19808
A similar translocation, described as t(1;4)(q42;q22), has been reported in one ALL patient (Behm et al., 1992).
44	57/F	White	47,XX,t(1;9)(p2?2;p2?4),+8[3]/46,XX[1]	M5a	de novo	6.7	47	3.1	27/86	NR	H/S	CR	127.6+	128.6+	AD 8525	LDAC 8525
A similar translocation, described as t(1;9)(p22;p23), has been reported in a patient with CML at the time of relapse following an alloSCT (Shah et al., 1992).
45	54/M	White	46,XY,t(1;9;12)(q31;p22;q21)[32]	M5a	de novo	11.7	28	53.1	88/94	-	LAD; S	CR	12.6	14	AD 9222	HIDAC/CY/E/AZ/MX 9222
The constitutional nature of this abnormality could not be excluded.
46	53/F	White	46,XX,t(1;19)(p12;q13.1)[18]/46,XX[2]	M4	de novo	7.6	64	0.9	27/39	-	No	R	NA	6.5	ADEx2 19808	NA
A similar translocation, described as t(1;19)(p13;q13), has been reported in one patient with ALL-L1 (Riesch et al., 2001).
47	45/F	White	46,XX,t(2;3)(q33;q25)[20]	M1	de novo	10.2	101	12.2	57/60	-	No	R	NA	24.3	ADEx2 9621	NA
The acquired, non-constitutional nature of the translocation has been confirmed by a cytogenetically normal result of phytohemagglutinin-stimulated blood analysis.
48	66/M	White	46,XY,t(4;14;8)(p16;q1?1.2;p21)[37]	M2	de novo	10	80	52.5	26/80	-	No	DA	NA	.5	AD 8221	NA
The constitutional nature of this abnormality could not be excluded.
49	75/F	White	46,XX,t(5;21)(p13;q22)[5]/46,XX[15]	M1	de novo	8.8	26	1.8	0/91	-	No	R	NA	5.5	ADE 9720	NA
50	55/F	White	46,XX,t(7;12)(p13;q24.1)[20]	M1	t-AML	9.2	52	46	67/82	+	No	CR	70+	70.9+	ADE 19808	B/E, AutoSCT 19808
A similar translocation, described as t(7;12)(p13;q23), has been reported in AML as part of a complex karyotype (Sierra et al., 2005). Only karyotypically normal cells were detected in a CR sample.
51	51/M	White	46,XY,t(7;19;12)(q11.2;q13.2;p11.2)[18]/46,XY[2]	M1	de novo	8.5	169	18.8	56/80	-	No	CR	29.2+	30.1+	AD/MP 10603	HIDAC/ MP 10603; AlloSCT
52	52/F	White	46,XX,t(7;22)(p15.3;q13)[24]/46,XX[6]	M2	de novo	8.8	72	1.5	36/44	-	No	CR	72.2	79.9	AD 9022	HIDAC/CY/E/AZ/MX 9022
53	56/F	His-panic	46,XX,t(8;14;16)(p11.2;q13;p13.1)[17]/46,XX[3]	M4	de novo	8.6	32	64.6	56/77	-	No	R	NA	1.4	ADEPx2 9621	NA
This translocation may represent a three-way variant of the known recurrent translocation in AML t(8;16)(p11;p13) (Mitelman et al., 2012).
54	34/M	White	46,XY,t(9;10)(p13;p12),del(20) (q12q13.3)[17]/46,XY[3]	M5b	de novo	9.8	61	74.1	90/38	-	No	R	NA	4.8	ADE 19808	NA
55	66/F	White	46,XX,t(9;13)(q21.1;q33)[23]	M2	de novo	11.9	33	4.6	14/31	-	No	DA	NA	.5	AD 8525	NA
This case was previously reported as part of a series of older AML patients (Farag et al., 2006). The constitutional nature of this abnormality could not be excluded.
56	50/F	White	46,XX,t(11;12)(q23;q12)[3]/ 47,idem,+21[11]/46,XX[6]	M0	de novo	7.8	141	18.4	55/78	-	No	CR	90+	91+	ADE 19808	HIDAC/E 19808, AlloSCT
A similar translocation, described as t(11;12)(q23;q13), has been reported in two patients with AML-M4 (Hashii et al., 2004; Yagi et al., 2003), and in CML (Sun et al., 2011).
57	50/F	White	46,XX,t(11;12)(q24;q24.2)[3]/46,XX[20]	M1	de novo	8.4	214	30.7	87/81	-	No	CR	67.2+	69.5+	ADEx2 19808	B/E, AutoSCT 19808
A similar translocation, described as t(11;12)(q23;q24), has been reported as a sole abnormality in AML-M0 (Cox et al., 2004) and as part of a complex karyotype in AML-M5a (Schoch et al., 2003). A translocation described as t(11;12)(q23-24;q24) has also been reported in ALL (Raimondi et al., 1989).
58	68/M	White	46,XY,t(11;19)(q21;q13)[22]/45,idem,−17[3]/46,XY[5]	M2	de novo	12.9	368	4.1	45/71	+	No	CR	41.9	45.6	ADx2 8525	IDAC 8525
59	82/M	White	46,XY,t(13;14)(q12;q24)[cp14]/47,idem,+4[4]/46,XY[1]	M2	de novo	10.8	85	33.2	74/63	-	S	CR	20.3	34.1	ADx2 10201	HIDAC 10201
60	52/F	White	46,XX,t(14;20)(q10;q10)[16]/46,XX[4]	M0	de novo	9.2	130	2.4	63/70	-	No	R	NA	1	ADEPx2 19808	NA
61	65/F	White	46,XX,t(16;18)(p11.2;q23)[19]/46,XX[1]	M4	de novo	8.8	149	5.2	2/34	-	No	CR	37.8	40.1	AD 10201	HIDAC 10201

Abbreviations: x2, two cycles of induction therapy; A, cytarabine; AD, cytarabine, daunorubicin; ADE, cytarabine, daunorubicin, etoposide; ADEP, cytarabine, daunorubicin, etoposide, valspodar; AI, cytarabine, idarubicin; AlloSCT, allogeneic stem cell transplantation; AML NOS, AML not otherwise specified; ATRA, all-trans-retinoic acid; AutoSCT, autologous stem cell transplantation; AZ, diaziquone; B, busulfan; BM, bone marrow; CY, cytoxan; CR, complete remission; D, daunorubicin; DA, died aplastic; DEC, decitabine; DFS, disease-free survival; E, etoposide; F, female; FAB, French-American-British classification; FLAG, fludarabine, cytarabine, filgrastim; H, hepatomegaly; Hb, hemoglobin; HIDAC, high-dose cytarabine; HSM, hepatosplenomegaly; I, idarubicin; IDAC, intermediate-dose cytarabine; L, l-asparaginase; LAD, lymphadenopathy; LDAC, low-dose cytarabine; M, male; mo, months; MP, midostaurin or placebo; MX, mitoxantrone; MY, mylotarg; NA, not applicable; NR, not reported; OS, overall survival; P, prednisone; PB, peripheral blood; Plts, platelet count; R, primary resistant disease; RD, relapsed AML; S, splenomegaly; t-AML, therapy-related AML; UAL, unclassifiable acute leukemia; V, vincristine; VA, valproic acid; WBC, white blood cell count.

^aAge, karyotype, hematologic and clinical characteristics are at the time of diagnosis of AML/MDS with the new recurrent translocation.

^bResponse to therapy for AML/MDS with new recurrent translocation (see footnote c).

^cInduction and post-remission therapy refer to initial treatment for patients with de novo AML/MDS or t-AML. For patients with relapsed AML, induction and post-remission therapy refer to treatment given at time of diagnosis of new recurrent translocation. The four- or five-digit number denotes a Cancer and Leukemia Group B [or Southwest Oncology Group (SWOG) in one instance, as indicated] protocol number a given patient was enrolled on as follows: 8525 (Mayer et al., 1994), 19808 (Kolitz et al., 2010), 10503 (Blum et al., 2010), 8721, 9311 (Szatrowski et al., 2003), SWOG 0106 (Petersdorf et al., 2009), 10105 (Gupta et al., 2006), 9222 (Moore et al., 2005), 8221 (Mayer et al., 1987), 9120 (Cassileth et al., 1998), 9022 (Moore et al., 1997), 8821 (Schiffer et al., 1991), 9621 (Kolitz et al., 2004), 9710 (Powell et al., 2011), 9720 (Baer et al., 2011), 10603, 10201 (Marcucci et al., 2007).