Optical Genome Mapping Helps to Identify BCR::JAK2 Rearrangement Arising from Cryptic Complex Chromosomal Aberrations: A Case Report and Literature Review
by
, , , and
Neelam Vanjari
1,
Guilin Tang
2,
Gokce A. Toruner
2,
Wei Wang
2,
Beenu Thakral
2,
Ming Zhao
1,
Bhavana J. Dave
3,
Joseph D. Khoury
3
,
L. Jeffrey Medeiros
2 and
Zhenya Tang
2,3,* 1
School of Health Professions, The University of Texas MD Anderson Cancer Center, Houston, TX 77015, USA
2
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77015, USA
3
Department of Pathology, Microbiology and Immunology, University of Nebraska Medical Center, Omaha, NE 68198, USA
*
Author to whom correspondence should be addressed.
Genes 2023, 14(12), 2188; https://doi.org/10.3390/genes14122188
Submission received: 17 November 2023
/
Revised: 28 November 2023
/
Accepted: 2 December 2023
/
Published: 8 December 2023
(This article belongs to the Section Cytogenomics)
Abstract
:We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with BCR::JAK2 rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible BCR rearrangement and a reflex JAK2 breakapart probe indicated JAK2 rearrangement, most likely partnered with BCR. Optical genome mapping (OGM) analysis confirmed BCR::JAK2 derived through an inv(9)(p24p13) after a t(9;22)(p13;q11.2) in this case. Due to the complexity of chromosomal aberrations, disruption and/or rearrangement of other genes such as KIF24::BCR, JAK2::KIF24/UBAP1, and CDK6:SOX9 were also identified by OGM. Although the functionality and clinical importance of these novel rearrangements were unknown, disruption of these genes might be associated with a poorer response to chemotherapy and disease progression. We also reviewed all cases with BCR::JAK2 rearrangement reported in the literature. In conclusion, a suspected t(9;22)/BCR::JAK2 rearrangement warrants further characterization with genomic assays such as OGM, whole chromosome sequencing, and RNA sequencing to explore other gene disruptions and/or rearrangements.
1. Introduction
Rearrangement between BCR, located at chromosome 22q11.2, and JAK2, located at chromosome 9p24.1 (BCR::JAK2), is a recurrent but infrequent chromosomal aberration. To date, 17 cases with confirmed BCR::JAK2 rearrangement have been reported in the literature, mostly in patients with myeloproliferative neoplasms, not otherwise specified (MPN-NOS) [1,2,3,4,5,6,7,8,9,10,11], but also in patients with acute myeloid leukemia (AML) [12], acute B-lymphoblastic leukemia (B-ALL) [13,14,15,16], and myeloid/lymphoid neoplasms with eosinophilia [10,17]. In some cases, the AML or B-ALL has transformed from an antecedent MPN [10,15,16]. At least from the chromosomal analysis results described in their reports, a simple and balanced t(9;22)(p24;q11.2)/BCR::JAK2 has been reported in most cases [1,2,4,6,7,12,16]. A three-way translocation, involving one more chromosome other than chromosomes 9 and 22, has been reported in some cases and most of these also showed a balanced three-way translocation [3,11,14,15]. An insertion, apparent ins(22;9)(q11;p24p13) [5] or cryptic ins(22;9)(q11;p24p24) [10], has been reported in two cases, whereas the underlying chromosomal aberration(s) related to BCR::JAK2 were not fully characterized and described in other cases [9,13,17].
Since both JAK2 and BCR are in an orientation of plus strand on chromosomal loci 9p and 22q, respectively, a simple, reciprocal t(9;22)(p24;q11.2) will generate a head-to-head (5′BCR::5′JAK2) and a tail-to-tail (3′BCR::3′JAK2) recombination that are insufficient to form an in-frame, functional 3′BCR::5′JAK2 or BCR::JAK2 fusion. Therefore, in those cases with morphologically balanced t(9;22) and/or three-way translocations, the BCR::JAK2 rearrangement must have been derived from a complex genomic rearrangement, such as translocation plus inversion, which might not be totally detected by standard chromosomal analysis. Here, we report a new BCR::JAK2 rearranged case that arose from complex aberrations involving chromosomes 9 and 22. Intensive FISH studies and the novel technology of optical genome mapping (OGM) analysis were applied to confirm BCR::JAK2 rearrangement and further characterize genome-wide structural variants (SVs) and copy number variants (CNVs) in this case. OGM analysis confirmed all findings detected by both chromosomal and FISH analyses and revealed several novel rearrangements/fusions which may be associated with disease progression.
2. Case Report
A 39-year-old man presented with a myeloproliferative/myelodysplastic syndrome (MPN/MDS) diagnosed at an outside institution. According to the submitted reports, the initial bone marrow examination showed 95% hypercellularity with grade I myelofibrosis without any increase in blasts. Conventional cytogenetic analysis of bone marrow (BM) showed 46,XY in six cells and then, in a subsequent specimen, t(7;17)(q22;q25),t(9;22)(p13;q11.2). BCR/ABL Dual Fusion (DF) FISH analysis showed a negative result for BCR::ABL1 rearrangement but did detect an extra BCR signal in 76% of analyzed cells. The patient received chemotherapy and ruxolitinib for 3 months but developed disease progression. He was then referred to our hospital in December 2022.
Bone marrow aspiration and biopsy showed acute myeloid leukemia (AML) with megakaryoblast differentiation and 25% blasts. The blasts were CD33+ and CD123+. Conventional chromosomal analysis revealed morphologically balanced t(7;17)(q21;q24) and t(9;22)(p24;q11.2) observed in all 20 cells analyzed (Figure 1A), and the karyotype was initially proposed as 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2) [18]. The Vysis BCR/ABL1/ASS1 Tri-Color DF FISH Probe (Abbott Molecular, Abbott Park, IL) was employed and did not detect BCR::ABL1 rearrangement, but an additional BCR signal was detected in all 200 cells analyzed (100%) (Figure 1B). Interestingly, one BCR (green) signal was located on the short (p) arm of the abnormal chromosome 9, der(9), and was very close to the centromere of der(9) as well, whereas a dim green signal was located on the der(22), indicating a gain of an additional green signal likely due to a BCR rearrangement. Vysis 5p15.2/5q35, CEP7/7q31, and TP53/CEP17 FISH tests were negative. Therefore, the CytoCell JAK2 breakapart FISH (OGT Inc., Tarrytown, NY, USA) was then reflexed with a positive result for JAK2 rearrangement (Figure 1C) in all 200 cells analyzed (100%). Both the split-apart 5′JAK2 (red) and 3′JAK2 (green) signals were located on the der(22), and the 3′JAK2 (green) was close to the centromere of the der(22), almost at the same place as the dim BCR signal mentioned above. This result suggested a BCR::JAK2 rearrangement, whereas the 5′JAK2 (red) signal was close to the telomere of the der(22) (Figure 1C). Taken together, a BCR::JAK2 rearrangement was postulated to have formed through two steps of chromosomal recombination: a t(9;22)(p13;q11.2) causing the BCR rearrangement suggested by BCR/ABL1/ASS1 FISH and an inversion of 9p on the der(22), inv(9)(p13p24), driving the JAK2 rearrangement confirmed by JAK2 BAP FISH, as well as very likely a BCR::JAK2 rearrangement that was later further confirmed by optical genome mapping (OGM) (see below). Therefore, the final chromosomal analysis result was reported as the following: 46,XY,t(7;17)(q21;q24),der(9)t(9;22)(p13;q11.2),der(22)t(9;22)inv(9)(p13p24) [20] by following the ISCN 2020 [18].
Ultra-high molecular weight genomic DNA extracted from the bone marrow aspirate specimen was subjected to direct labeling and staining (DLS) and was then assessed by OGM, as reported previously [19]. OGM analysis detected co-existence of t(9;22)(p24.1;q11.23)/BCR::JAK2, t(9;22)(p13.3;q11.23)/KIF24::BCR and an intra-chromosomal fusion between 9p24.1 and 9p13.3 with a JAK2::KIF24/UBAP1 (Figure 2 and Table 1). In general, an intra-chromosomal fusion detected by OGM can be theoretically caused by any recombination between two chromosomal homologs (such as translocation and insertion) or an intra-homolog recombination (such as inversion, segmental deletion, and/or duplication). Both KIF24 and UBAP1 are located at 9p13.3, and they are adjacent to each other with a small overlap of approximately 140 base pairs (bp). Interestingly, OGM also detected t(7;17)(21.13;q24) without any gene fusion, t(7;17)(21.2;q24)/CDK6:SOX9, and an intra-chromosomal fusion between 7q21.13 and 7q21.2 via deletion of 7q21.13q21.2 of approximately 3 Mbp or del(7)(q21.13q21.2)(chr7: 89,828,122–92,814,090) (Figure 2 and Table 2). In summary, in correlation with chromosomal and FISH analysis findings, OGM analysis showed that der(9) was formed through t(9;22)(p13.3;q11.23) with KIF24::BCR rearrangement and der(22) was derived from t(9;22) followed by an inv(9)(p24p13.3) with BCR::JAK2 rearrangement on the centromeric side and JAK2::KIF24/UBAP1 rearrangement on the telomeric side, as illustrated in Figure 3. The t(7;17)(21.13;q24) and the t(7;17)(21.2;q24) cannot be distinguished by conventional chromosomal analysis at the current level of resolution (<550 band level), and the microdeletion of 7q21.13q21.2 causing these translocations involving two different band levels of 7q is also cryptic for chromosomal analysis. The patient was treated with cladribine and cytarabine in our hospital, but his disease progressed rapidly and he died 3 months later. At his last workup, JAK2 BAP FISH was still positive (33%), but chromosomal analysis could not be repeated due to a hypocellular bone marrow specimen.
3. Discussion
Although BCR::JAK2 rearrangement is relatively rare in MPNs, detection/confirmation of this mutation may qualify affected patients for targeted therapy, such as ruxolitilib alone [13,14] and/or in a combination with BCL2 inhibitors such as venetoclax [11]. To the best of our knowledge, there are 17 cases with confirmed BCR::JAK2 rearrangement in the literature, with an additional 5 cases with t(9;22)(p24;q11.2) and suspicious BCR::JAK2 rearrangement solely based on karyotype only and/or limited FISH studies (Table 3) [20,21,22,23,24]. Interestingly, 4 of the 5 cases suspicious for BCR::JAK2 rearrangement also showed a morphologically balanced t(9;22)(p24;q11.2). In fact, the B-ALL case reported by Tirado et al. [20] had a JAK2 rearrangement due to an additional JAK2 signal located on the der(22), but the authors could not prove a simultaneous BCR rearrangement or a BCR::JAK2 fusion by intensive FISH studies. Chen et al. [24] also reported a B-ALL case with t(9;22)(p24;q11.2). However, they failed to detect either JAK2::BCR or BCR::JAK2 fusion transcripts in that case. By adding the case with BCR::JAK2 confirmed by intensive FISH and OGM analyses in this study, the database of BCR::JAK2-positive cases has been increased to a total of 18 cases. This is also the second BCR::JAK2-positive AML case transformed from a MPN-NOS [12] (Table 3).
BCR::JAK2 rearrangement via an insertion of 3′JAK2 into the BCR, either as an apparent [5] or as a cryptic [10] chromosomal aberration, has been reported in two cases. An insertion of the 5′BCR into the ABL1 is also theoretically capable of generating a functional BCR::JAK2 rearrangement, but no such cases like this have been reported. However, for a t(9;22)(p24;11.2) with suspicious BCR::JAK2 rearrangement to occur, as demonstrated in our case, a complex chromosomal recombination must have brought BCR and JAK2 into juxtaposition to generate a pathogenic 5′BCR::3′JAK2 or BCR::JAK2 fusion. Therefore, the t(9;22)(p24;11.2) and other three-way translocations involving 9p24 and 22q11.2 in the previously reported cases were most likely described solely according to the morphology of chromosomal aberrations. It is relevant to mention that BCR::JAK2 fusions have been confirmed by RT-PCR, Sanger Sequencing, and/or other methods in the majority of these cases (Table 3). Interestingly, several isoforms of BCR::JAK2 fusion transcripts have been isolated, e.g., BCR::JAK2/E1::E17 (6 cases), BCR::JAK2/E1::E19 (5 cases), BCR::JAK2/E1::E15 (3 cases), BCR::JAK2/E14::E11 (1 case), and BCR::JAK2/E13::E17 (1 case). Co-existence of two isoforms has been observed in 3 cases. The clinical significance of these isoforms remains unknown. For our case reported in this study, a BCR::JAK2/E1::E17 (Table 1) is postulated by applying the breakpoints of 5′BCR and 3′JAK2 obtained by OGM into the UCSC Genome Browser, respectively.
The complexity of chromosomal aberrations usually indicates the possibility of mutations simultaneously involving multiple genes, in addition to BCR and JAK2. Although chromosomal analysis was reported as a simple abnormal karyotype with t(9;22)(p24;q11.2) in a B-ALL case, Chen et al. [16] showed a co-existence of JAK2::PPM1F rearrangement and PRAMENP::BCR rearrangement by whole genome sequencing (WGS). A novel JAK2::PPM1F/E16::E2 fusion was further identified by RT-PCR and Sanger sequencing, although it was postulated as non-functional due to induction of a stop codon in the fusion gene. In a myeloid/lymphoid neoplasm with eosinophilia case reported by Snider et al. [10], as further characterized by mate-pair sequencing, involvement of four derivative chromosomes (der(8), der(9), and two copies of der(22)) to form the BCR::JAK2 rearrangement and a novel PCM::JAK2/E7::E9E10 rearrangement were identified. In the case we report here, the co-existing KIF24::BCR and JAK2::KIF24/UBAP1 rearrangements were detected by OGM. Although a functional fusion transcript from these two novel rearrangements cannot be determined, KIF24 and/or UBAP1 were certainly disrupted in our case.
As a novel technology, OGM has played an important role in further characterizing cryptic chromosomal aberrations and confirming BCR::JAK2 rearrangement. OGM analysis also revealed various novel rearrangements such as KIF24::BCR, JAK2::KIF24/UBAP1, and CDK6:SOX9 and microdeletion of del(7)(q21.13q21.2) in the case we reported. All these novel findings were not detected by routine chromosomal analysis and targeted FISH, and these abnormalities might be associated with a poor response to chemotherapy and disease progression from MPN-NOS to AML, as occurred in this patient. As suggested by Snider and others, all cases with confirmed and/suspected BCR::JAK2 rearrangement warrant analysis using integrated genomic approaches such as WGS, RNA sequencing, and OGM to fully characterize the underlying complex chromosomal aberrations.
In summary, cases with BCR::JAK2 rearrangement are infrequent and chromosomal aberrations producing a functional BCR::JAK2 fusion can be complicated. Very likely, disruption and/or rearrangement of other important gene(s) can be co-existent. Utilizing integrated genomic approaches such as OGM, WGS, and/or RNA sequencing is strongly recommended.
Author Contributions
Conceptualization, Z.T.; methodology, G.T., G.A.T. and Z.T.; validation, G.T., G.A.T., M.Z. and Z.T.; writing—original draft preparation, N.V. and Z.T.; writing—review and editing, G.T., G.A.T., W.W., B.T., M.Z., B.J.D., J.D.K. and L.J.M. All authors have read and agreed to the published version of the manuscript.
Funding
This research received no external funding.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of The University of Texas MD Anderson Cancer Center (PA 2022-0218. Date of approval: 3/30/2022).
Informed Consent Statement
Informed consent was obtained from the subject involved in the study.
Data Availability Statement
Data are contained within the article.
Conflicts of Interest
The authors declare no conflict of interest.
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Figure 1.
Chromosomal and FISH analyses in this case. (A) A representative karyogram with abnormal chromosomes 7, 9, 17, and 22 pointed out by arrows. (B) Representative BCR/ABL1/ASS1 metaphase FISH (left) and inverted (right) images. Red arrows: ABL1/ASS1 probe; Green: BCR probe. The der(9) has an ABL1/ASS1 (red) signal on its q arm and a BCR (green) signal on its p arm, while the der(22) has a dim BCR (green) signal on it. (C) Representative JAK2 BAK metaphase FISH (left) and inverted (right) images. Red arrows: 5′JAK2 signal; Green: 3′JAK2 signal probe; Orange: intact JAK2 signal. The normal 9 has an intact JAK2 signal on it, while the der(22) has the split-apart 5′JAK2 (red) and 3′JAK2 (green) signals on it.
Figure 1.
Chromosomal and FISH analyses in this case. (A) A representative karyogram with abnormal chromosomes 7, 9, 17, and 22 pointed out by arrows. (B) Representative BCR/ABL1/ASS1 metaphase FISH (left) and inverted (right) images. Red arrows: ABL1/ASS1 probe; Green: BCR probe. The der(9) has an ABL1/ASS1 (red) signal on its q arm and a BCR (green) signal on its p arm, while the der(22) has a dim BCR (green) signal on it. (C) Representative JAK2 BAK metaphase FISH (left) and inverted (right) images. Red arrows: 5′JAK2 signal; Green: 3′JAK2 signal probe; Orange: intact JAK2 signal. The normal 9 has an intact JAK2 signal on it, while the der(22) has the split-apart 5′JAK2 (red) and 3′JAK2 (green) signals on it.
Figure 2.
The OGM analysis in this case. (Left) OGM Circos plot illustrates the chromosomal aberrations in this case. (Right) The enlarged views of the areas containing chromosomes 7 to 9 indicated two types of t(7;17)s, two types of t(9;22), and intra-chromosomal fusions involving chromosomes 7 and 9, respectively. Please see detailed information of these chromosomal aberrations in Table 1 and Table 2.
Figure 2.
The OGM analysis in this case. (Left) OGM Circos plot illustrates the chromosomal aberrations in this case. (Right) The enlarged views of the areas containing chromosomes 7 to 9 indicated two types of t(7;17)s, two types of t(9;22), and intra-chromosomal fusions involving chromosomes 7 and 9, respectively. Please see detailed information of these chromosomal aberrations in Table 1 and Table 2.
Figure 3.
Illustration of the aberrations and locations of affected genes on chromosomes 9 (blue color) and 22 (red color). (Left) Normal chromosomes 9 and 22 and locations of certain genes on them. (Right) der(22) and der(9) and locations of certain gene rearrangements on them. der: derivative.
Figure 3.
Illustration of the aberrations and locations of affected genes on chromosomes 9 (blue color) and 22 (red color). (Left) Normal chromosomes 9 and 22 and locations of certain genes on them. (Right) der(22) and der(9) and locations of certain gene rearrangements on them. der: derivative.
Table 1.
The detailed information of aberrations involving chromosome 9 and 22, including breakpoints, confidence, VAF, putative gene fusion, and ISCN called by using Bionano Access Software (v1.7) (the Genome Reference Consortium Human Reference 38 (GRCh38) has been applied).
Table 1.
The detailed information of aberrations involving chromosome 9 and 22, including breakpoints, confidence, VAF, putative gene fusion, and ISCN called by using Bionano Access Software (v1.7) (the Genome Reference Consortium Human Reference 38 (GRCh38) has been applied).
| SV Type | Chr Involved #1 | Chr Involved #2 | Breakpoint #1 (bp) | Breakpoint #1 (bp) | Confidence | VAF | Putative Gene Fusion | ISCN |
|---|---|---|---|---|---|---|---|---|
| Transl. | 9 | 22 | 34,271,272 | 23,219,177 | 0.98 | 0.48 | KIF24-BCR | ogm[GRCh38) t(9;22)(p13.3;q11.23) |
| Transl. | 9 | 22 | 5,079,902 | 23,205,817 | 0.99 | 0.5 | JAK2-BCR | ogm[GRCh38) t(9;22)(p24.1;q11.23) |
| intrachr_fusion | 9 | 22 | 5,077,416 | 34,246,297 | 0.99 | 0.47 | JAK2-UBAP1/KIF24 | ogm[GRCh38) fus(9;9)(p24.1;p13.3) |
SV: structural variant; Chr: chromosome; bp: base pair; Transl.: translocation; intrachr_fusion: intra-chromosomal fusion; fus: fusion; VAF: variant allele frequency.
Table 2.
The detailed information of aberrations involving chromosomes 7 and 17 detected by OGM analysis (the Genome Reference Consortium Human Reference 38 (GRCh38) has been applied).
Table 2.
The detailed information of aberrations involving chromosomes 7 and 17 detected by OGM analysis (the Genome Reference Consortium Human Reference 38 (GRCh38) has been applied).
| SV Type | Chr Involved #1 | Chr Involved #2 | Breakpoint #1 (bp) | Breakpoint #1 (bp) | Confidence | VAF | Putative Gene Fusion | ISCN |
|---|---|---|---|---|---|---|---|---|
| Transl. | 7 | 17 | 108,464,953 | 72,155,558 | 1 | 0.45 | ogm[GRCh38) t(7;17)(q31.1;q24.3) | |
| Transl. | 7 | 17 | 92,814,090 | 72,155,558 | 1 | 0.38 | CDK6-SOX9 | ogm[GRCh38) t(7;17)(q21.2;q24.3) |
| intrachr_fusion | 7 | 7 | 89,954,704 | 108,465,844 | 0.94 | 0.45 | ogm[GRCh38) fus(7;7)(q21.13;q31.1) |
SV: structural variant; Chr: chromosome; bp: base pair; Transl.: translocation; intrachr_fusion: intra-chromosomal fusion; fus: fusion; VAF: variant allele frequency.
Table 3.
Twenty-three cases with confirmed and suspicious BCR::JAK2 rearrangement reported in the literature, including the case reported in this study.
Table 3.
Twenty-three cases with confirmed and suspicious BCR::JAK2 rearrangement reported in the literature, including the case reported in this study.
| Year | Authors | Age/Sex | Diagnosis | Chromosomal Analysis | FISH Analysis | Confirmation of BCR::JAK2 | BCR::ABL1 Isoform(s) |
|---|---|---|---|---|---|---|---|
| 2005 | Griesinger et al. [1] | 63 yo, F | MPN-NOS | 46,XX,del(7)(q22q36)[21]/47,idem,t(9;22)(p24;q11.2),+19[5] | BCRx3 by BCR/ABL1 DF FISH | Yes. RT-PCR and Sanger Seq | E1::E19 |
| 2008 | Cirmena et al. [12] | 67 yo, F | AML * | 46,XX,t(9;22)(p24;q11) | BCRx3 by BCR/ABL1 DF FISH | Yes. RT-PCR and Sanger Seq | E14::E11 |
| 2008 | Lane et al. [2] | 44 yo, M | MPN-NOS | 46,XY,t(9;22)(p24;q11.2) [23]/46,XY[27] | BCR/ABL1 DF FISH-negative | Yes. RT-PCR and Sanger Seq | E1::E17 |
| 2011 | Impera et al. [3] | 54 yo, F | MPN-NOS | 46,XX,t(9;18;22)(p23;p11.3;q11.2)[18]/46,XX[2] | BCR/ABL1 FISH-negative, other intensive FISH studies | Yes. SNP array, RT-PCR, and Sanger Seq | E1::E15 and E1::E17 |
| 2012 | Cuesta-Dominguez et al. [13] | 55 yo, F | B-ALL | 49,XY,+X,+2,+4,−9,−11,+19,add(19)(q13),+20,−22,+mar[24]/46,XY[1] | BCR/JAK2 fusion FISH-positive | Yes. RT-PCR and Sanger seq | E1::E19 |
| 2012 | Elnaggar et al. [4] | 84 yo, M | MPN-NOS | 46,XX,t(9;22)(p24;q11.2) | BCRx3 by BCR/ABL1 DF FISH | Yes. RT-PCR and Sanger seq | E1::E19 |
| 2012 | Roberts et al. [14] | 2 yo, M | B-ALL | 47,XY,+2,del(2)(p23),t(3;22;9)(p12;q11.2; p24)[10]/46,XY[2] | n/a | Yes. WGS, RNA Seq, RT-PCR, and Sanger Seq | E1::E15 and E1::E17 |
| 2013 | Xu et al. [5] | 28 yo, M | MPN-NOS | ins(22;9)(q11;p13p24) | JAK2 BAP-positive | Yes. RT-PCR and Sanger seq | E1::E19 |
| 2015 | Chamseddine et al. [6] | 49 yo, M | MPN-NOS | 46,Y,t(9;22)(p24;q11)[12/20]/47,idem,+der(22)t(9;22)[2/20]/46,XY [6/20] | BCRx3 by BCR/ABL1 DF FISH; JAK2 BAP FISH-positive | Yes. RT-PCR and Sanger seq | E13::E17 |
| 2015 | Schwaab et al. [7] | ? | MPN-NOS | t(9;18)(p24;q12),der(18)ins(22)(BCR) | JAK2 BAP-positive | Yes. RT-PCR and Sanger seq | E1::E17 |
| 2016 | Duployez et al. [15] | 58 yo, M | B-ALL * | 47,XY,+8,t(9;22;15)(p24;q11;q21)(at MPN-U stage) | JAK2 BAP FISH-positive | Yes. RT-PCR and Sanger seq | E1::E17 |
| 2016 | He et al. [8] | 36 yo, F | MPN-NOS | Complex karyotype with multiple rearrangements involving chromosome 22, including a non-classical, unbalanced t(9;22) resulting in a derivative 9 from a t(9;22) and a dicentric rearrangement involving chromosomes 22 and 10. | BCRx3 by BCR/ABL1 DF FISH; JAK2 BAP FISH-positive | Yes. RT-PCR and Sanger seq | E1::E15 and E1::E17 |
| 2019 | Millett et al. [9] | 53 yo, M | MPN-NOS ** | n/a | JAK2 BAP-positive | Yes. RT-PCR | n/a |
| 2020 | Snider et al. [10] | 59 yo, M | Myeloid/lymphoid neoplasm with eosinophilia | 46,XY,t(3;21)(q21;q22)[10]/47,XY,+11[5]/46,XY[5] | JAK2 BAP-positive | Yes. Mate-pair seq | n/a |
| 2020 | Thakral et al. [17] | 31 yo, M | Myeloid neoplasm with eosinophilia | 46,XY,add(22)(q11.2)[13]/46,XY[7] | BCRx3 by BCR/ABL1 DF FISH | Yes. RNA seq | n/a |
| 2021 | Chen et al. [16] | 32 yo, M | B-ALL * | 46,XY,t(9;22)(p24;q11.2)[15]/46,XY[5] (with IKZF1 deletion) | BCR signal on der(9) by BCR/ABL1 DF FISH | Yes. WGS, RT-PCR, and Sanger Seq | E1::E19 |
| 2021 | Lap et al. [11] | 54 yo, M | MPN-NOS ** | 46,XY,del(6)(p21.2p24),t(22;9;11)(q11.2,p24,p11.2)[11]/46XY,del(9)[9] | BCRx3 by BCR/ABL1 DF FISH; JAK2 BAP FISH-positive | Yes. RT-PCR and Sanger seq | E1::E19 |
| 2010 | Tirado et al. [20] | 14 yo, M | B-ALL | 46,XY,t(9;22)(p24;q11.2)[14]/46,XY[6] | JAK2 BAP-positive | No | |
| 2011 | Angelova et al. [21] | 53 yo, M | MPN-NOS/MDS with Eos and baso | 47,XY,dup(3)(q25q27),+8,der(9)t(9;22)(p24;q11),dup(14)(q24q32),+14,−22[13]/47,XY,dup(1)(p13p22),dup(3)(q25q27),+8,add(8)(q24),der(9)t(9;22)(p24;q11),−22,+mar [6]/47,XY,dup(3)(q25q27),+8,t(9;22)(p24;q11),dup(14)(q24q32),+14,−21[1] | No | No | n/a |
| 2013 | Bellesso et al. [22] | 54 yo, M | MPN-NOS | 46,XY,t(9;22)(p24;q11.2) | BCR/ABL1 DF, BCR/PDGFR DF FISH-negative | No | n/a |
| 2015 | Kantarcioglu et al. [23] | 64 yo, F | MDS | 47,X,-X,+3,t(9;22)(p24;q11.2),+18[3]/46,XX[17] | BCR/ABL1 DF | No | |
| 2020 | Chen et al. [24] | 45 yo, M | B-ALL | 46,XY,t(9;22)(p24;q11.2)[9]/46,XY[2] | No | No JAK2-BCR and BCR-JAK2 fusion was detected by RT-PCR | |
| This study | Vanjari et al. | 39 yo, M | AML * | 46,XY,t(7;17)(q21;q24),der(9)t(9;22)(p13;q11.2),der(22)t(9;22)inv(9)(p13p24)[20] | BCRx3 by BCR/ABL1/ASS1 DF FISH; JAK2 BAP FISH-positive | Yes. OGM | E1:E17 |
* Transformed from previous MPN-NOS. ** Previous history of HL and chemotherapy.
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Vanjari, N.; Tang, G.; Toruner, G.A.; Wang, W.; Thakral, B.; Zhao, M.; Dave, B.J.; Khoury, J.D.; Medeiros, L.J.; Tang, Z. Optical Genome Mapping Helps to Identify BCR::JAK2 Rearrangement Arising from Cryptic Complex Chromosomal Aberrations: A Case Report and Literature Review. Genes 2023, 14, 2188. https://doi.org/10.3390/genes14122188
AMA Style
Vanjari N, Tang G, Toruner GA, Wang W, Thakral B, Zhao M, Dave BJ, Khoury JD, Medeiros LJ, Tang Z. Optical Genome Mapping Helps to Identify BCR::JAK2 Rearrangement Arising from Cryptic Complex Chromosomal Aberrations: A Case Report and Literature Review. Genes. 2023; 14(12):2188. https://doi.org/10.3390/genes14122188
Chicago/Turabian StyleVanjari, Neelam, Guilin Tang, Gokce A. Toruner, Wei Wang, Beenu Thakral, Ming Zhao, Bhavana J. Dave, Joseph D. Khoury, L. Jeffrey Medeiros, and Zhenya Tang. 2023. "Optical Genome Mapping Helps to Identify BCR::JAK2 Rearrangement Arising from Cryptic Complex Chromosomal Aberrations: A Case Report and Literature Review" Genes 14, no. 12: 2188. https://doi.org/10.3390/genes14122188
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