Fluorescence in situ hybridization (FISH) is a powerful tool in diverse areas of
basic research as well as in clinical medicine. This molecular cytogenetic technique
has revolutionized our ability to localize specific DNA sequences within interphase
chromatin and metaphase chromosomes and to identify both structural and numerical
chromosome changes. While FISH is becoming one of the most used cytochemical staining
technique in many labs, the new PNA-FISH approach is quickly gaining speed. The
method of using DNA analogues to recognize and bind specific nucleic acid sequences
in situ to detect chromosomal abnormalities and repeat structure in the human genome
have quickly become an important tool in biological assays.
Bio-Synthesis offers on-demand PNA FISH probes in either a red or a green fluorophore
(Texas Red, FITC, Cy3, Alexa series respectively). Each FISH probe is supplied in
5 or 10 nmole quantities (100-200 tests), shipped lyophilized and is HPLC purified.
Large volume is available, contact us for custom PNA
manufacturing.
PNA probes can be used in many hybridization applications as natural or synthetic DNA probes, but PNA probes offer distinctive advantages over DNA probes. First, the neutral backbone allows PNA/DNA binding to occur more rapidly and tightly than DNA/DNA binding at lower ionic strength conditions that disfavor reannealing of complimentary genomic strands. This advantage is particularly important for in situ hybridization experiments which target repetitive sequences. Both the length and the repetitive nature of the target sequences will affectively favor renaturation over hybridization with labeled probes. Second, the high affinity of PNA probes to DNA also constitutes an important feature for chromosomal analysis. As studies have demonstrated, PNA probes can discriminate between two centromeric DNA repeats that differ by only a single base pair1,2, whereas standard FISH probes are unable to discriminate sequences with a single base resolution. Additional benefits of using PNAs in FISH applications are lower background signals and unlimited stability of the probe mixture3. PNA probes are compatible with a wide range of reporter molecules and fluorochromes, including fluoresceine, rhodamine, as well as cyanine and Alexa dyes in a wide variety of colors.
Comparison of PNA and DNA
| Criteria |
PNA |
DNA |
| Hybridization affinity with DNA |
At least 1 °C higher Tm per base |
- |
| Hybridization rate with DNA |
100 - 5000 times faster |
- |
| Salt concentration for hybridization |
Independent |
Dependent |
| Tm for each single mismatch |
Lowering 15°C |
Lowering 10°C |
| Chemical stability |
Stable |
Unstable or moderate |
| Biological stability |
Stable to nuclease and protease |
Degradation by nuclease |
| Thermal stability |
Good |
Moderate |
| Water solubility |
Restricted solubility enhanced by use of appropriate linkers |
Soluble |
| Probe length for diagnostic use |
13 - 18 bases |
20-30 bases |
Reference/Citing:
1.Chen C, Hong YK, Ontiveros SD, Egholm M, Strauss WM: Single base discrimination of CENP-B repeats on mouse and human chromosomes with PNA-FISH. Mamm Genome 1999; 10:13-18.
2.Chen C, Wu B, Wei T Egholm M, Strauss WM: Unique chromosome identification and sequence-specific structural analysis with short PNA oligomers. Mamm Genome 2000; 11:384-391
3.Williams et al.: PNA fluorescent in situ hybridization for rapid microbiology and cytogenetic analysis. Humana Press 2002; 181-193
4.P. Paulasova et al.: The peptide nucleic acids as probes for chromosomal analysis: application to human oocytes, polar bodies and preimplantation embryos. Molecular Human Reproduction 2004; 10:467-472
5.D. Griend at al.: Dual-Label Centromere and Telomere FISH Identifies Human, Rat, and Mouse Cell Contribution to Multispecies Recombinant Urogenital Sinus Xenografts. The Prostate 2009; 69:1557-156
Telomere PNA FISH Probes
Telomeres consist of repeats of TTAGGG and CCCTAA sequence at the ends of vertebrate chromosome. These repeats have played an important roles in essential cellular processes like replication, malignant transformation, cellular aging and believed to play a role in senescence and cancer.
Bio-Synthesis provides on-demand Telomere PNA FISH probes as an invaluable tool to researcher seeking solution to detect human telomere sequences using fluorophore-labeled PNA. This method provides excellent quantitation as the fluorescence intensity directly correlates to the length of the telomeres.
Bio-Synthesis offers on-demand Telomere PNA FISH probes in either a red or a green fluorophore (Texas Red, FITC, FAM, TAMRA Cy3, Alexa series respectively). Each FISH probe is supplied in 5 or 10 nmole quantities (100-200 tests), shipped lyophilized and HPLC purified. Large volume is available, contact us for custom PNA manufacturing.
Telomere C FISH Probe
| Item No. |
Product Name |
Sequences |
Quantity |
Price |
| PNA1001-005 |
PNA Telomere C FISH FAM Probe |
FAM-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1001-010 |
PNA Telomere C FISH FAM Probe |
FAM-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1002-005 |
PNA Telomere C FISH FITC Probe |
FITC-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1002-010 |
PNA Telomere C FISH FITC Probe |
FITC-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1003-005 |
PNA Telomere C FISH TAMRA Probe |
TAMRA-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1003-010 |
PNA Telomere C FISH TAMRA Probe |
TAMRA-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1004-005 |
PNA Telomere C FISH CY3 Probe |
CY3-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1004-010 |
PNA Telomere C FISH CY3 Probe |
CY3-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1005-005 |
PNA Telomere C FISH CY5 Probe |
CY5-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1005-010 |
PNA Telomere C FISH CY5 Probe |
CY5-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1006-005 |
PNA Telomere C FISH Alexa 488 Probe |
Alexa 488-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1006-010 |
PNA Telomere C FISH Alexa 488 Probe |
Alexa 488-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1007-005 |
PNA Telomere C FISH Alexa 555 Probe |
Alexa 555-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1007-010 |
PNA Telomere C FISH Alexa 555 Probe |
Alexa 555-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1008-005 |
PNA Telomere C FISH Alexa 610 Probe |
Alexa 610-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1008-010 |
PNA Telomere C FISH Alexa 610 Probe |
Alexa 610-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1009-005 |
PNA Telomere C FISH Alexa 647 Probe |
Alexa 647-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1009-010 |
PNA Telomere C FISH Alexa 647 Probe |
Alexa 647-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1010-005 |
PNA Telomere C FISH Texas Red Probe |
Texas Red-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1010-010 |
PNA Telomere C FISH Texas Red Probe |
Texas Red-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1011-005 |
PNA Telomere C FISH Biotin Probe |
Biotin-OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1011-010 |
PNA Telomere C FISH Biotin Probe |
Biotin-OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1012-005 |
PNA Telomere C FISH Unlabeled Probe |
OO-(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1012-010 |
PNA Telomere C FISH Unlabeled Probe |
OO-(CCCTAA)3 |
10 nmoles |
Contact Us |
| PNA1013-005 |
PNA Telomere C FISH Naked Sequence |
(CCCTAA)3 |
5 nmoles |
Contact Us |
| PNA1013-010 |
PNA Telomere C FISH Naked Sequence |
(CCCTAA)3 |
10 nmoles |
Contact Us |
Telomere G FISH Probe
| Item No. |
Product Name |
Product Description |
Quantity |
Price
|
| PNA1050-005 |
PNA Telomere G FISH FAM Probe |
FAM-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1050-010 |
PNA Telomere G FISH FAM Probe |
FAM-OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1051-005 |
PNA Telomere G FISH FITC Probe |
FITC-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1051-010 |
PNA Telomere G FISH FITC Probe |
FITC-OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1052-005 |
PNA Telomere G FISH TAMRA Probe |
TAMRA-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1052-010 |
PNA Telomere G FISH TAMRA Probe |
TAMRA-OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1053-005 |
PNA Telomere G FISH CY3 Probe |
CY3-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1053-010 |
PNA Telomere G FISH CY3 Probe |
CY3-OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1054-005 |
PNA Telomere G FISH CY5 Probe |
CY5-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1054-010 |
PNA Telomere G FISH CY5 Probe |
CY5-OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1055-005 |
PNA Telomere G FISH Alexa 488 Probe |
Alexa 488-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1055-010 |
PNA Telomere G FISH Alexa 488 Probe |
Alexa 488-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1056-005 |
PNA Telomere G FISH Alexa 555 Probe |
Alexa 555-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1056-010 |
PNA Telomere G FISH Alexa 555 Probe |
Alexa 555-OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1057-005 |
PNA Telomere G FISH Alexa 610 Probe |
Alexa 610-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1057-010 |
PNA Telomere G FISH Alexa 610 Probe |
Alexa 610-OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1058-005 |
PNA Telomere G FISH Alexa 647 Probe |
Alexa 647-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1058-010 |
PNA Telomere G FISH Alexa 647 Probe |
Alexa 647-OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1059-005 |
PNA Telomere G FISH Texas Red Probe |
Texas Red-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1059-010 |
PNA Telomere G FISH Texas Red Probe |
Texas Red-OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1060-005 |
PNA Telomere G FISH Biotin Probe |
Biotin-OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1060-010 |
PNA Telomere G FISH Biotin Probe |
Biotin-OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1061-005 |
PNA Telomere G FISH Unlabeled Probe |
OO-(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1061-010 |
PNA Telomere G FISH Unlabeled Probe |
OO-(TTAGGG)3 |
10 nmoles |
Contact Us |
| PNA1062-005 |
PNA Telomere G FISH Naked Sequence |
(TTAGGG)3 |
5 nmoles |
Contact Us |
| PNA1062-010 |
PNA Telomere G FISH Naked Sequence |
(TTAGGG)3 |
10 nmoles |
Contact Us |
Centromere PNA FISH Probes
Centromeres are special structures of eukaryotic chromosomes that hold sister chromatid together and ensure proper chromosome segregation during cell division. These repeated sequences play an important role in centromere mitotic recombination and its consequences for centromeric function. PNA-FISH centromere probes have been used to visualize and quantify directed against aberration in these interspersed alpha-satellite chromosomal related diseases, such as, aneuploidies (trisomies), polysomy in human.
Bio-Synthesis offers on-demand centromere PNA FISH probes in either a red or a green fluorophore (FAM, FITC, TAMRA, Cy3, Alexa series respectively). Each FISH probe is supplied in 5 or 10 nmole quantities (100-200 tests), shipped lyophilized and HPLC purified. Large volume is available, contact us for custom PNA manufacturing.
Centromere FISH Probe (Human)
| Prod. No. |
Human Centromere FISH Probe |
Product Description |
Quantity |
Price |
| PNA1100-005 |
PNA Centromere FISH FAM Probe |
FAM-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1100-010 |
PNA Centromere FISH FAM Probe |
FAM-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1101-005 |
PNA Centromere FISH FITC Probe |
FITC-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1101-010 |
PNA Centromere FISH FITC Probe |
FITC-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1102-005 |
PNA Centromere FISH TAMRA Probe |
TAMRA-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1102-010 |
PNA Centromere FISH TAMRA Probe |
TAMRA-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1103-005 |
PNA Centromere FISH CY3 Probe |
CY3-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1103-010 |
PNA Centromere FISH CY3 Probe |
CY3-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1104-005 |
PNA Centromere FISH CY5 Probe |
CY5-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1104-010 |
PNA Centromere FISH CY5 Probe |
CY5-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1105-005 |
PNA Centromere FISH Alexa 488 Probe |
Alexa488-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1105-010 |
PNA Centromere FISH Alexa 488 Probe |
Alexa488-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1106-005 |
PNA Centromere FISH Alexa 555Probe |
Alexa 555-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1106-010 |
PNA Centromere FISH Alexa 555Probe |
Alexa 555-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1107-005 |
PNA Centromere FISH Alexa 610 Probe |
Alexa 610-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1107-010 |
PNA Centromere FISH Alexa 610 Probe |
Alexa 610-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1108-005 |
PNA Centromere FISH Alexa 647 Probe |
Alexa 647-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1108-010 |
PNA Centromere FISH Alexa 647 Probe |
Alexa 647-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1109-005 |
PNA Centromere FISH Texas Red Probe |
Texas Red-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1109-010 |
PNA Centromere FISH Texas Red Probe |
Texas Red-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1110-005 |
PNA Centromere FISH Biotin Probe |
Biotin-OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1110-010 |
PNA Centromere FISH Biotin Probe |
Biotin-OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1111-005 |
PNA Centromere FISH Unlabeled Probe |
OO-ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1111-010 |
PNA Centromere FISH Unlabeled Probe |
OO-ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
| PNA1112-005 |
PNA Centromere FISH Naked Sequence |
ATTCGTTGGAAACGGGA |
5 nmoles |
Contact Us |
| PNA1112-010 |
PNA Centromere FISH Naked Sequence |
ATTCGTTGGAAACGGGA |
10 nmoles |
Contact Us |
Centromere FISH Probe (Mouse)
| Prod. No. |
Mouse Centromere FISH Probe |
Product Description |
Quantity |
Price |
| PNA1150-005 |
Mouse PNA Centromere FISH FAM Probe |
FAM-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1150-010 |
Mouse PNA Centromere FISH FAM Probe |
FAM-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1151-005 |
Mouse PNA Centromere FISH FITC Probe |
FITC-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1151-010 |
Mouse PNA Centromere FISH FITC Probe |
FITC-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1152-005 |
Mouse PNA Centromere FISH TAMRA Probe |
TAMRA-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1152-010 |
Mouse PNA Centromere FISH TAMRA Probe |
TAMRA-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1153-005 |
Mouse PNA Centromere FISH CY3 Probe |
CY3-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1153-010 |
Mouse PNA Centromere FISH CY3 Probe |
CY3-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1154-005 |
Mouse PNA Centromere FISH CY5 Probe |
CY5-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1154-010 |
Mouse PNA Centromere FISH CY5 Probe |
CY5-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1155-005 |
Mouse PNA Centromere FISH Alexa488 Probe |
Alexa 488-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1155-010 |
Mouse PNA Centromere FISH Alexa488 Probe |
Alexa 488-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1156-005 |
Mouse PNA Centromere FISH Alexa 555 Probe |
Alexa 555-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1156-010 |
Mouse PNA Centromere FISH Alexa 555 Probe |
Alexa 555-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1157-005 |
Mouse PNA Centromere FISH Alexa 610 Probe |
Alexa 610-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1157-010 |
Mouse PNA Centromere FISH Alexa 610 Probe |
Alexa 610-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1158-005 |
Mouse PNA Centromere FISH Alexa 647 Probe |
Alexa 647-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1158-010 |
Mouse PNA Centromere FISH Alexa 647 Probe |
Alexa 647-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1159-005 |
Mouse PNA Centromere FISH Texas Red Probe |
Texas Red-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1159-010 |
Mouse PNA Centromere FISH Texas Red Probe |
Texas Red-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1160-005 |
Mouse PNA Centromere FISH Biotin Probe |
Biotin-OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1160-010 |
Mouse PNA Centromere FISH Biotin Probe |
Biotin-OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1161-005 |
Mouse PNA Centromere FISH Unlabeled Probe |
OO-CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1161-010 |
Mouse PNA Centromere FISH Unlabeled Probe |
OO-CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
| PNA1162-005 |
Mouse PNA Centromere FISH Naked Sequence |
CACAAAGAAGTTTCTGAG |
5 nmoles |
Contact Us |
| PNA1162-010 |
Mouse PNA Centromere FISH Naked Sequence |
CACAAAGAAGTTTCTGAG |
10 nmoles |
Contact Us |
Reference/Citing:
1. S. Selvaraju et al.: Peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) assay for specific detection of Mycobacterium immunogenum and DNA-FISH assay for analysis of pseudomonads in metalworking fluids and sputum. Molecular and Cellular Probes 2008, Vol 22, Issue 5-6, P273-280
2. E. Akbay et al.: Differential Roles of Telomere Attrition in Type I and II Endometrial Carcinogenesis. American Society for Investigative Pathology 2008, 173:536-544
3. B Steensel at al: TRF2 Protects Human Telomeres from End-to-End Fusions. Cell 1998, Vol. 92, 401-413.
4. J. Kenny at al.: Detection of viable Yersinia pestis by fluorescence in situ hybridization using peptide nucleic acid probes, Journal of Microbiological Methods 2008 Vol 75, Issue 2, P293-301
5. A. Meeker at al.: Telomere Length Assessment in Human Archival Tissues Combined Telomere Fluorescence in Situ Hybridization and Immunostaining. American Society for Investigative Pathology 2002, 160(4): 1259-1268
6. K. Shimizu-Kohno at al.: Detection of HTLV-1 by means of HBZ gene in situ hybridization in formalin-fixed and paraffin-embedded tissues. Cancer Science 102 (7):1432-1436
7. E. Sloand at al.: T cell immune responses to Wilms tumor 1 protein in myelodysplasia responsive to immunosuppressive therapy. Blood 2010
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