De nove Philadelphia chromosome-positive myelodysplastic syndromes with complex karyotype and p230 BCR::ABL fusion transcript: a case report with a literature review

Figures & data

Figure 1. A. The bone marrow (BM) hyperplasia at diagnosis of Myelodysplastic syndromes (MDS) was obviously active with a myeloid: erythroid ratio of 0.67:1 with dysplasia, such as megaloblastic changes,abnormal chromatin clumping, and multinuclearity. B. The BM smear was hypercellular with myeloid preponderance associated with left shift maturation and trilineage dysplasia. C. The BM smear was hypercellular with 28.8% of myeloblast and dysplasia. D. The fluorescence in situ hybridization analysis with painting probes for BCR gene (green arrows) and ABL(red arrows) showed atypical BCR/ABL-positive signals. The BCR/ABL fusion signals were marked by yellow arrows. E. G-banded karyotype of the patient: 46XY, der(9)t(9;17)(q34;q21),add(17)(q21),der(22),?t(9;22)(q34;q11),inc[cp4]/46,XY[16]. The abnormal chromosomes are indicated by arrows. F. Quantitative reverse transcriptase polymerase chain reaction analysis revealed the BCR/ABL to ABL transcript ratio of 23.02%.

Table 1. Clinical characteristics of patients with de novo Philadelphia-positive myelodysplastic syndrome.

No./Sex/Age	WBC/HB/PLT	FAB classification	Cytogenetic (Ph%)	Disease course	OS (m)	Ref.
1/F/49	6.5/82/ 42.5	MDS-RA	46,XX,t(9;22)(q34;q11)[3]/46,XX[5] (37.5%)	Progressed to AML 32 m later and died in another 1 m.	33 died	[15]
		32 m→AML	46,XX,t(9;22)(q34;q11)[1]/46,XX[1] (50%)
2/F/70	6.4/95/316	MDS-RARS	46,XX,t(9;22)(q34;q11)[3]/46,XX[12](20%)	Stable and alive for over 45 m.	45 alive	[16]
3/M/70	NA/NA/ NA	MDS-RARS	45,XY,−5,−7,−8,+19,+mar[12]/45,XY,−5,−7,−8,−19,+mar, t(9;22)(q34;q11)[4] (25%).	progressed to and died of AML in another 4 m.	4 died	[17]
		4 m→AML	NA
4/M/85	3/61/286	MDS-RAEB	46,XY,t(9;22)(q34;q11)[22]	Progressed to RAEBt in 19 m and died in another 2 m.	21 died	[18]
		19 m→MDS-RAEBt	NA
5/M/56	2.4/48/ 350	MDS-RA	45.XY,−1,−2,−12,+der(1)t(1;12)(p32; q13),t(9;22)(q34;q11),der(11)(9?;11) (q22?;p15),+der (X)t(X;1)(q22;p13)	Progressed to AML in 51 m and died in another 1 m.	52 died	[19]
		51 m→AML	45.XY,−1,−2,−12,+der(1)t(1;12)(p32;q 13),t(9;22)(q34;q11),der(11)(9?;11) (q22?;p15), +der(X)t(X;1)(q22;p13)
6/M/30	5.8/125/ 30	MDS-RA	46,XY, t(9;22)(q34;q11)[45]/46,XY[1] (98.7%)	died of intracranial hemorrhage in 21 m.	21 died	[20]
7/M/64	6.9/78/68	MDS-RAEB	47,XY,+8,t(9:22)(q34;q11)[6]/46,XY[7](46.2%)	Progressed to AML in 9 m and died in another 16 days.	9 died	[12]
		9 m→AML	47,XY,+8,t(9:22)(q34;q11) p190 BCR::ABL +
8/F/67	34/115/ 111	MDS-RAEB	46,XX,t(9:22)(q34;q11)[29]/46,XX[1] (96.7%)	IM therapy started in 23 m,cCR in 3 m and mCR in 14 m.	37 alive	[21]
		23 m→AML	47,XY,+8,t(9:22)(q34;q11)[30] (100%)
9/F/66	4.2/84/ 150	MDS-RAEB	47,XX,+8,t(9;22;16)(q34;q11.2;q23)[4]/46,XX,idem,der(12)t(12;17)(p11.2;q11.2)[7]/46, XX[9] (20%)	Progressed to GS of skin in 9 m and died 1 m later.	10 died	[14]
		9 m→GS	NA
10/M/67	2.7/104/ 52	MDS-RA	45,XY,+3,–5,–7,–7,−20,+2mar/45, XY, +3,–4,–8,–9,–11,–18,–20,–21,−21, + 4mar,+breaks BCR::ABL + (67%) by FISH and PCR	IM therapy 2 wk and withdrawl due to cytopenias worsened,progressed to RAEB2 within 1 year and died.	12 died	[22]
		within 1 year→ MDS-RAEB2	45,XY,−4,−6,−7,−18,+3mar[6]/46XY[4]
11/M/65	NA/NA/NA	MDS-RAEB2	44,XY,del(5)(q31),−7,del(12) (p12),−14,−16,+mar[cp20] / p190 BCR::ABL + (0.33%) by FISH and PCR	Died of lung cancer shortly after MDS.	NA died	[23]
12/M/74	5.4/NA/NA	MDS-MLD	46,XY,t(9:22)[4]/46,XY[16]/p210 BCR::ABL(24.1180%)	mCR after 4 m of Das therapy, died of respireatory failure in 7 m.	7 died	[24]
13/F/68	3.2/61/98	MDS-RARS	46,XX,der(11)t(11;14)(?;q?)[7]/46,XX,der(16;19)(p10;p10),+19[3]/46,XX[13] /p190 BCR::ABL (0.8%) by FISH and PCR	Died of multiple organ failure in 3 wk.	0.75 died	[25]
14/F/72	4.29/42/ 112	MDS(5q-)	46,XX,del(5)(q15q35)[11]/46,XX,del(5)(q15q35),t(9;22)((p13;q11.2)[3]/46,XX[27]/ (7.3%)	hCR and BCR::ABL (10.18%) after LEN therapy 6 m.	6 alive	[26]
15/F/55	15.7/103/ 10	MDS-RAEB1	45,XX, −4,t(9;22)(q34;q11.2)	Died within 1 m.	1 Died	[27]
16/M/31	2.8/47/54	MDS-RAEB2	44–45,XY,+X,der(4),-5,der(7),-7,-8, t(9;22)(q34;q11.2),-15,+22,+mar1[cp20]	Died in 1 wk.	0.25 died	[27]
17/M/74	1.7/92/61	MDS-MLD	46,XY,der(9)t(9;17)(q34;q21),add(17)(q21),der(22),t(9;22)(q34;q11),inc[cp4]/46,XY[16] (3.0%)	IM therapy 5 wk af­ter progression to CML and progresse­d to AML in anoth­er 4 m, PR to VEN + AZA	24 died	Our case
		14 m→CML 18 m→AML	45–46,XY,−3,der(6),der(7), t(9;22)(q34 ;q11),−13,−15,−18,+19,+21,+mar1[cp3] / 46, XY[3] (20%)

Abbreviations: M, male; F, female; m, month; wk, week; MDS, myelodysplastic syndrome; CML, chronic myeloid leukemia; AML, acute myeloid leukemia; RA, refractory anemia; RARS, refractory anemia with ringed sideroblasts; MLD, multilineage dysplasia; RAEB, refractory anemia with excess of blasts; RAEBt, refractory anemia with excess of blasts in transformation; GS, granulocytic sarcoma; hCR, hematologic complete remission; mCR, molecular complete remission; PR, partial remission; OS, Overall survival; IM, Imatinib; DSA, Dasatinib; LEN, Lenalidomide; VEN, venetoclax; AZA, azacitidine; NA, not available

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