User login
Antibodies Part 3: In whose corner is genome editing’s best cut-man sitting?
We are in the midst of a revolution in genome editing. Science now exists in “AC,” or after CRISPR. Able to speedily and efficiently make genomic cuts with surgical precision, CRISPR/Cas9 is used almost ubiquitously now in the scientific community to study and alter DNA across fields ranging from medicine to agriculture to zoology. The possibilities of the biological and therapeutic implications are seemingly endless, as are the important ethical implications of their impact. Likely because of the latter, CRISPR technology has made its way from publications like Science and Nature into the lay public domains of Newsweek and NBC News.
In fact, CRISPR technology made its way into one of my favorite podcasts, WNYC’s “Radio Lab” in June 20151. The episode was entitled “Antibodies Part 1,” perhaps assuming that other technologies would also be discussed later although that has never happened. Actually, in an update early this year, the podcast jokingly addressed never moving on to “Part 2,” then followed with an update on how far CRISPR technology has progressed. Putting aside the technological advances and the early clinical applications, as well as the immense ethical considerations, CRISPR technology faces a new controversy, not one from a white coat but rather from a black robe.
In her CommonHealth blog2, Carey Goldberg of WBUR Boston Public Radio compared the case with the bout between undefeated Muhammad Ali and undefeated Joe Frazier at New York’s Madison Square Garden. Both men had legitimate claims to the title of World Heavyweight Champion. What transpired is now known as the “Fight of the Century.”
The analogy is apt. Boxing is about speed and control. Ali dominated the first three rounds with his jab, a punch that is both offensive with its attack and defensive in keeping one’s opponent at a distance. Dr. Doudna and her collaborator Emmanuelle Charpentier, PhD, published their work first (Science. 2012 Aug 17;337[6096]:816-21)3. UC Berkeley filed their patent first in May 2012.
Boxing is about timing and opportunity. Under the barrage of Ali’s jabs, Frazier found an inside position and caught Ali with a left hook. Dr. Zhang’s work followed closely after but had previously applied the technology in murine and human cells (Science. 2013 Feb 15; 339[6121]:819-23)4. The Broad Institute used this key difference to apply for its own patents under expedited review, which were granted in April 2014.
Boxing is about a punch and a counterpunch. Though fatigued, Ali continued to connect with combination punches. Frazier’s left hook pummeled Ali’s jaw. UC Berkeley filed an interference motion to invalidate the Broad Institute patent claim on the basis that the extension to eukaryotic cells was “obvious” based on the published work by Dr. Doudna’s group. In February, USPTO ruled that the Broad patent application may proceed, citing “patentably distinct subject matter.” Initial reports had indicated that Berkeley may appeal the decision, but no official filings have been made public.
Like the Fight of the Century, this case may go the distance and be decided by the judges. In a unanimous decision, Joe Frazier won the first of three epic bouts. The final scorecard is not known in the patent disputes; on March 28, the European Patent Office announced it will grant the patent application on behalf of Dr. Doudna and Dr. Charpentier.
Much like a prizefight, Wall Street has also been taking bets on who will prevail, with CRISPR-based biotech backing both sides mirroring the mid-bout odds, just as Ali dominated early with the jab, until Frazier evened the match with a left hook to the jaw. Ali fell to his knee on the canvas in the 11th round; will the European Patent Office decision prove to be a slip or a decisive knockdown? With so much at stake, the only assurance is that, as with the Ali-Frazier bout, there is likely more fighting to be done.
References:
1. Radio Lab
2. CommonHealth blog
3. Jinek M, et al., A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012 Aug 17;337(6096):816-21.
4. Le Cong et al., Multiplex genome engineering using CRISPR/Cas Systems. Science. 2013 Feb 15;339(6121):819-23. Multiplex genome engineering using CRISPR/Cas Systems.
Science. 2017 Feb 15: Round one of CRISPR patent legal battle goes to the Broad Institute.
StreetInsider.com: CRISPR Therapeutics (CRSP) says EPO to grant CRISPR/Cas gene editing patent.
vinya@mskcc.org
On Twitter @thedoctorisvin
Dr. Viny is with the Memorial Sloan-Kettering Cancer Center, N.Y., where he is a clinical instructor, is on the staff of the leukemia service, and is a clinical researcher in the Ross Levine Lab. Contact Dr. Viny at vinya@mskcc.org.
We are in the midst of a revolution in genome editing. Science now exists in “AC,” or after CRISPR. Able to speedily and efficiently make genomic cuts with surgical precision, CRISPR/Cas9 is used almost ubiquitously now in the scientific community to study and alter DNA across fields ranging from medicine to agriculture to zoology. The possibilities of the biological and therapeutic implications are seemingly endless, as are the important ethical implications of their impact. Likely because of the latter, CRISPR technology has made its way from publications like Science and Nature into the lay public domains of Newsweek and NBC News.
In fact, CRISPR technology made its way into one of my favorite podcasts, WNYC’s “Radio Lab” in June 20151. The episode was entitled “Antibodies Part 1,” perhaps assuming that other technologies would also be discussed later although that has never happened. Actually, in an update early this year, the podcast jokingly addressed never moving on to “Part 2,” then followed with an update on how far CRISPR technology has progressed. Putting aside the technological advances and the early clinical applications, as well as the immense ethical considerations, CRISPR technology faces a new controversy, not one from a white coat but rather from a black robe.
In her CommonHealth blog2, Carey Goldberg of WBUR Boston Public Radio compared the case with the bout between undefeated Muhammad Ali and undefeated Joe Frazier at New York’s Madison Square Garden. Both men had legitimate claims to the title of World Heavyweight Champion. What transpired is now known as the “Fight of the Century.”
The analogy is apt. Boxing is about speed and control. Ali dominated the first three rounds with his jab, a punch that is both offensive with its attack and defensive in keeping one’s opponent at a distance. Dr. Doudna and her collaborator Emmanuelle Charpentier, PhD, published their work first (Science. 2012 Aug 17;337[6096]:816-21)3. UC Berkeley filed their patent first in May 2012.
Boxing is about timing and opportunity. Under the barrage of Ali’s jabs, Frazier found an inside position and caught Ali with a left hook. Dr. Zhang’s work followed closely after but had previously applied the technology in murine and human cells (Science. 2013 Feb 15; 339[6121]:819-23)4. The Broad Institute used this key difference to apply for its own patents under expedited review, which were granted in April 2014.
Boxing is about a punch and a counterpunch. Though fatigued, Ali continued to connect with combination punches. Frazier’s left hook pummeled Ali’s jaw. UC Berkeley filed an interference motion to invalidate the Broad Institute patent claim on the basis that the extension to eukaryotic cells was “obvious” based on the published work by Dr. Doudna’s group. In February, USPTO ruled that the Broad patent application may proceed, citing “patentably distinct subject matter.” Initial reports had indicated that Berkeley may appeal the decision, but no official filings have been made public.
Like the Fight of the Century, this case may go the distance and be decided by the judges. In a unanimous decision, Joe Frazier won the first of three epic bouts. The final scorecard is not known in the patent disputes; on March 28, the European Patent Office announced it will grant the patent application on behalf of Dr. Doudna and Dr. Charpentier.
Much like a prizefight, Wall Street has also been taking bets on who will prevail, with CRISPR-based biotech backing both sides mirroring the mid-bout odds, just as Ali dominated early with the jab, until Frazier evened the match with a left hook to the jaw. Ali fell to his knee on the canvas in the 11th round; will the European Patent Office decision prove to be a slip or a decisive knockdown? With so much at stake, the only assurance is that, as with the Ali-Frazier bout, there is likely more fighting to be done.
References:
1. Radio Lab
2. CommonHealth blog
3. Jinek M, et al., A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012 Aug 17;337(6096):816-21.
4. Le Cong et al., Multiplex genome engineering using CRISPR/Cas Systems. Science. 2013 Feb 15;339(6121):819-23. Multiplex genome engineering using CRISPR/Cas Systems.
Science. 2017 Feb 15: Round one of CRISPR patent legal battle goes to the Broad Institute.
StreetInsider.com: CRISPR Therapeutics (CRSP) says EPO to grant CRISPR/Cas gene editing patent.
vinya@mskcc.org
On Twitter @thedoctorisvin
Dr. Viny is with the Memorial Sloan-Kettering Cancer Center, N.Y., where he is a clinical instructor, is on the staff of the leukemia service, and is a clinical researcher in the Ross Levine Lab. Contact Dr. Viny at vinya@mskcc.org.
We are in the midst of a revolution in genome editing. Science now exists in “AC,” or after CRISPR. Able to speedily and efficiently make genomic cuts with surgical precision, CRISPR/Cas9 is used almost ubiquitously now in the scientific community to study and alter DNA across fields ranging from medicine to agriculture to zoology. The possibilities of the biological and therapeutic implications are seemingly endless, as are the important ethical implications of their impact. Likely because of the latter, CRISPR technology has made its way from publications like Science and Nature into the lay public domains of Newsweek and NBC News.
In fact, CRISPR technology made its way into one of my favorite podcasts, WNYC’s “Radio Lab” in June 20151. The episode was entitled “Antibodies Part 1,” perhaps assuming that other technologies would also be discussed later although that has never happened. Actually, in an update early this year, the podcast jokingly addressed never moving on to “Part 2,” then followed with an update on how far CRISPR technology has progressed. Putting aside the technological advances and the early clinical applications, as well as the immense ethical considerations, CRISPR technology faces a new controversy, not one from a white coat but rather from a black robe.
In her CommonHealth blog2, Carey Goldberg of WBUR Boston Public Radio compared the case with the bout between undefeated Muhammad Ali and undefeated Joe Frazier at New York’s Madison Square Garden. Both men had legitimate claims to the title of World Heavyweight Champion. What transpired is now known as the “Fight of the Century.”
The analogy is apt. Boxing is about speed and control. Ali dominated the first three rounds with his jab, a punch that is both offensive with its attack and defensive in keeping one’s opponent at a distance. Dr. Doudna and her collaborator Emmanuelle Charpentier, PhD, published their work first (Science. 2012 Aug 17;337[6096]:816-21)3. UC Berkeley filed their patent first in May 2012.
Boxing is about timing and opportunity. Under the barrage of Ali’s jabs, Frazier found an inside position and caught Ali with a left hook. Dr. Zhang’s work followed closely after but had previously applied the technology in murine and human cells (Science. 2013 Feb 15; 339[6121]:819-23)4. The Broad Institute used this key difference to apply for its own patents under expedited review, which were granted in April 2014.
Boxing is about a punch and a counterpunch. Though fatigued, Ali continued to connect with combination punches. Frazier’s left hook pummeled Ali’s jaw. UC Berkeley filed an interference motion to invalidate the Broad Institute patent claim on the basis that the extension to eukaryotic cells was “obvious” based on the published work by Dr. Doudna’s group. In February, USPTO ruled that the Broad patent application may proceed, citing “patentably distinct subject matter.” Initial reports had indicated that Berkeley may appeal the decision, but no official filings have been made public.
Like the Fight of the Century, this case may go the distance and be decided by the judges. In a unanimous decision, Joe Frazier won the first of three epic bouts. The final scorecard is not known in the patent disputes; on March 28, the European Patent Office announced it will grant the patent application on behalf of Dr. Doudna and Dr. Charpentier.
Much like a prizefight, Wall Street has also been taking bets on who will prevail, with CRISPR-based biotech backing both sides mirroring the mid-bout odds, just as Ali dominated early with the jab, until Frazier evened the match with a left hook to the jaw. Ali fell to his knee on the canvas in the 11th round; will the European Patent Office decision prove to be a slip or a decisive knockdown? With so much at stake, the only assurance is that, as with the Ali-Frazier bout, there is likely more fighting to be done.
References:
1. Radio Lab
2. CommonHealth blog
3. Jinek M, et al., A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science. 2012 Aug 17;337(6096):816-21.
4. Le Cong et al., Multiplex genome engineering using CRISPR/Cas Systems. Science. 2013 Feb 15;339(6121):819-23. Multiplex genome engineering using CRISPR/Cas Systems.
Science. 2017 Feb 15: Round one of CRISPR patent legal battle goes to the Broad Institute.
StreetInsider.com: CRISPR Therapeutics (CRSP) says EPO to grant CRISPR/Cas gene editing patent.
vinya@mskcc.org
On Twitter @thedoctorisvin
Dr. Viny is with the Memorial Sloan-Kettering Cancer Center, N.Y., where he is a clinical instructor, is on the staff of the leukemia service, and is a clinical researcher in the Ross Levine Lab. Contact Dr. Viny at vinya@mskcc.org.
FOUND IN TRANSLATION Minimal nomenclature and maximum sensitivity complicate MRD measures
In hematologic malignancies, there is a deep and direct connection between each individual patient, that patient’s symptoms, the visible cells that cause the disease, and the direct measurements and assessments of those cells. The totality of these factors helps to determine the diagnosis and treatment plan. As a butterfly needle often is sufficient for obtaining a diagnostic tumor biopsy, it is not surprising that these same diagnostic techniques are now standardly being used to monitor disease response.
The techniques differ in their limits of detection, however. With sequencing depths able to reliably detect variant allele frequencies of less than 10%, even when patients’ overt leukemia may no longer be detectable, clinicians may be left to ponder what to do with persistent “preleukemic” or “rising clones.”1-3
These patients, now more appropriately stratified for risk of recurrence, are in desperate need of better care algorithms. Standard MRD assessment by flow cytometric analysis is able to detect less than 1 x 10-4 cells. While it can be applied to most patients, its sensitivity will likely be surpassed by new and emerging genomic assays. Real time quantitative polymerase chain reaction (RT-qPCR) and next generation sequencing (NGS) require a leukemia-specific abnormality but have the potential for far greater sensitivity with deeper sequencing techniques.
Long-term follow up data in acute promyelocytic leukemia (APL) provides the illustrative example where morphologic remission is not durable in the setting of a persistent PML-RARa transcript and therapeutic goals for PCR negativity irrespective of morphology are standard. Pathologic fusion proteins are ideal for marker-driven therapy, but are found in only about 50% of patients, mainly those with APL and Philadelphia chromosome-positive leukemias.
With driver mutations identified in the majority of patients, we can be hopeful that NGS negativity may be a useful clinical endpoint. In work presented at ASH 2016 by Bartlomiej M Getta, MBBS, of Memorial Sloan Kettering Cancer Center, New York, and his colleagues, patients with concordant MRD positivity by flow cytometry and NGS had inferior outcomes, even after allogeneic transplant, compared to patients with MRD positivity on one assay but not both.5 Nonetheless, caution should be taken in early adoption of NGS as a independent marker of MRD status for two main reasons: 1) False positives and lack of standardization make current interpretation difficult. 2) The presence of “preleukemic” clones remains enigmatic – and no matter the nomenclature used, can a DNMT3A or IDH-mutant clone really be deemed “clonal hematopoiesis of indeterminate potential” when a patient has already had clonal transformation?
Conversely, not all patients reported in the work by Klco2 and Getta ultimately relapse. Thus, while it would be preferred to clear all mutant clones, as a therapeutic goal this likely would subject many patients to unnecessary toxicity. One half of the patients reported by Getta were disease free at a year with concordant flow and NGS positive MRD while patients with NGS positivity alone had outcomes equivalent to those of MRD-negative patients, highlighting that certain persistent clones in NGS-only, MRD-positive patients might be amenable to immunotherapy, either with checkpoint inhibitors or allogeneic transplant. Insight into which clones remain quiescent and which are more sinister will require more investigation, but there does seem to be an additive role to NGS-positivity, whereby all MRD is not created equal and the precision and clinical utility of MRD status will likely take on nuanced nomenclature.
References
1. Jan, M. et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Science Translational Medicine 4, 149ra118, doi: 10.1126/scitranslmed.3004315 (2012).
2. Klco, J. M. et al. Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia. JAMA 2015;314:811-22. doi: 10.1001/jama.2015.9643.
3. Wong, T. N. et al. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. Blood 2016;127:893-7. doi: 10.1182/blood-2015-10-677021 (2016).
4. Lane, A. A. et al. Results from Ongoing Phase II Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD), Abstract 215, ASH 2016.
5. Getta, B. M. et al. Multicolor Flow Cytometry and Multi-Gene Next Generation Sequencing Are Complimentary and Highly Predictive for Relapse in Acute Myeloid Leukemia Following Allogeneic Hematopoietic Stem Cell Transplant, Abstract 834, ASH 2016.
Dr. Viny is with the Memorial Sloan-Kettering Cancer Center, New York, where he is a clinical instructor, on the staff of the leukemia service, and a clinical researcher in The Ross Levine Lab. Contact Dr. Viny at vinya@mskcc.org.
In hematologic malignancies, there is a deep and direct connection between each individual patient, that patient’s symptoms, the visible cells that cause the disease, and the direct measurements and assessments of those cells. The totality of these factors helps to determine the diagnosis and treatment plan. As a butterfly needle often is sufficient for obtaining a diagnostic tumor biopsy, it is not surprising that these same diagnostic techniques are now standardly being used to monitor disease response.
The techniques differ in their limits of detection, however. With sequencing depths able to reliably detect variant allele frequencies of less than 10%, even when patients’ overt leukemia may no longer be detectable, clinicians may be left to ponder what to do with persistent “preleukemic” or “rising clones.”1-3
These patients, now more appropriately stratified for risk of recurrence, are in desperate need of better care algorithms. Standard MRD assessment by flow cytometric analysis is able to detect less than 1 x 10-4 cells. While it can be applied to most patients, its sensitivity will likely be surpassed by new and emerging genomic assays. Real time quantitative polymerase chain reaction (RT-qPCR) and next generation sequencing (NGS) require a leukemia-specific abnormality but have the potential for far greater sensitivity with deeper sequencing techniques.
Long-term follow up data in acute promyelocytic leukemia (APL) provides the illustrative example where morphologic remission is not durable in the setting of a persistent PML-RARa transcript and therapeutic goals for PCR negativity irrespective of morphology are standard. Pathologic fusion proteins are ideal for marker-driven therapy, but are found in only about 50% of patients, mainly those with APL and Philadelphia chromosome-positive leukemias.
With driver mutations identified in the majority of patients, we can be hopeful that NGS negativity may be a useful clinical endpoint. In work presented at ASH 2016 by Bartlomiej M Getta, MBBS, of Memorial Sloan Kettering Cancer Center, New York, and his colleagues, patients with concordant MRD positivity by flow cytometry and NGS had inferior outcomes, even after allogeneic transplant, compared to patients with MRD positivity on one assay but not both.5 Nonetheless, caution should be taken in early adoption of NGS as a independent marker of MRD status for two main reasons: 1) False positives and lack of standardization make current interpretation difficult. 2) The presence of “preleukemic” clones remains enigmatic – and no matter the nomenclature used, can a DNMT3A or IDH-mutant clone really be deemed “clonal hematopoiesis of indeterminate potential” when a patient has already had clonal transformation?
Conversely, not all patients reported in the work by Klco2 and Getta ultimately relapse. Thus, while it would be preferred to clear all mutant clones, as a therapeutic goal this likely would subject many patients to unnecessary toxicity. One half of the patients reported by Getta were disease free at a year with concordant flow and NGS positive MRD while patients with NGS positivity alone had outcomes equivalent to those of MRD-negative patients, highlighting that certain persistent clones in NGS-only, MRD-positive patients might be amenable to immunotherapy, either with checkpoint inhibitors or allogeneic transplant. Insight into which clones remain quiescent and which are more sinister will require more investigation, but there does seem to be an additive role to NGS-positivity, whereby all MRD is not created equal and the precision and clinical utility of MRD status will likely take on nuanced nomenclature.
References
1. Jan, M. et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Science Translational Medicine 4, 149ra118, doi: 10.1126/scitranslmed.3004315 (2012).
2. Klco, J. M. et al. Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia. JAMA 2015;314:811-22. doi: 10.1001/jama.2015.9643.
3. Wong, T. N. et al. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. Blood 2016;127:893-7. doi: 10.1182/blood-2015-10-677021 (2016).
4. Lane, A. A. et al. Results from Ongoing Phase II Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD), Abstract 215, ASH 2016.
5. Getta, B. M. et al. Multicolor Flow Cytometry and Multi-Gene Next Generation Sequencing Are Complimentary and Highly Predictive for Relapse in Acute Myeloid Leukemia Following Allogeneic Hematopoietic Stem Cell Transplant, Abstract 834, ASH 2016.
Dr. Viny is with the Memorial Sloan-Kettering Cancer Center, New York, where he is a clinical instructor, on the staff of the leukemia service, and a clinical researcher in The Ross Levine Lab. Contact Dr. Viny at vinya@mskcc.org.
In hematologic malignancies, there is a deep and direct connection between each individual patient, that patient’s symptoms, the visible cells that cause the disease, and the direct measurements and assessments of those cells. The totality of these factors helps to determine the diagnosis and treatment plan. As a butterfly needle often is sufficient for obtaining a diagnostic tumor biopsy, it is not surprising that these same diagnostic techniques are now standardly being used to monitor disease response.
The techniques differ in their limits of detection, however. With sequencing depths able to reliably detect variant allele frequencies of less than 10%, even when patients’ overt leukemia may no longer be detectable, clinicians may be left to ponder what to do with persistent “preleukemic” or “rising clones.”1-3
These patients, now more appropriately stratified for risk of recurrence, are in desperate need of better care algorithms. Standard MRD assessment by flow cytometric analysis is able to detect less than 1 x 10-4 cells. While it can be applied to most patients, its sensitivity will likely be surpassed by new and emerging genomic assays. Real time quantitative polymerase chain reaction (RT-qPCR) and next generation sequencing (NGS) require a leukemia-specific abnormality but have the potential for far greater sensitivity with deeper sequencing techniques.
Long-term follow up data in acute promyelocytic leukemia (APL) provides the illustrative example where morphologic remission is not durable in the setting of a persistent PML-RARa transcript and therapeutic goals for PCR negativity irrespective of morphology are standard. Pathologic fusion proteins are ideal for marker-driven therapy, but are found in only about 50% of patients, mainly those with APL and Philadelphia chromosome-positive leukemias.
With driver mutations identified in the majority of patients, we can be hopeful that NGS negativity may be a useful clinical endpoint. In work presented at ASH 2016 by Bartlomiej M Getta, MBBS, of Memorial Sloan Kettering Cancer Center, New York, and his colleagues, patients with concordant MRD positivity by flow cytometry and NGS had inferior outcomes, even after allogeneic transplant, compared to patients with MRD positivity on one assay but not both.5 Nonetheless, caution should be taken in early adoption of NGS as a independent marker of MRD status for two main reasons: 1) False positives and lack of standardization make current interpretation difficult. 2) The presence of “preleukemic” clones remains enigmatic – and no matter the nomenclature used, can a DNMT3A or IDH-mutant clone really be deemed “clonal hematopoiesis of indeterminate potential” when a patient has already had clonal transformation?
Conversely, not all patients reported in the work by Klco2 and Getta ultimately relapse. Thus, while it would be preferred to clear all mutant clones, as a therapeutic goal this likely would subject many patients to unnecessary toxicity. One half of the patients reported by Getta were disease free at a year with concordant flow and NGS positive MRD while patients with NGS positivity alone had outcomes equivalent to those of MRD-negative patients, highlighting that certain persistent clones in NGS-only, MRD-positive patients might be amenable to immunotherapy, either with checkpoint inhibitors or allogeneic transplant. Insight into which clones remain quiescent and which are more sinister will require more investigation, but there does seem to be an additive role to NGS-positivity, whereby all MRD is not created equal and the precision and clinical utility of MRD status will likely take on nuanced nomenclature.
References
1. Jan, M. et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Science Translational Medicine 4, 149ra118, doi: 10.1126/scitranslmed.3004315 (2012).
2. Klco, J. M. et al. Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia. JAMA 2015;314:811-22. doi: 10.1001/jama.2015.9643.
3. Wong, T. N. et al. Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML. Blood 2016;127:893-7. doi: 10.1182/blood-2015-10-677021 (2016).
4. Lane, A. A. et al. Results from Ongoing Phase II Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD), Abstract 215, ASH 2016.
5. Getta, B. M. et al. Multicolor Flow Cytometry and Multi-Gene Next Generation Sequencing Are Complimentary and Highly Predictive for Relapse in Acute Myeloid Leukemia Following Allogeneic Hematopoietic Stem Cell Transplant, Abstract 834, ASH 2016.
Dr. Viny is with the Memorial Sloan-Kettering Cancer Center, New York, where he is a clinical instructor, on the staff of the leukemia service, and a clinical researcher in The Ross Levine Lab. Contact Dr. Viny at vinya@mskcc.org.