Cancer Family
Malignant Bone Marrow Neoplasm
CI-CAN-00000226Explore in graph →
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Cancer Family
CI-CAN-00000226Explore in graph →
Variants & evidence
1,124 evidence items mapped to this entity or its descendants, grouped by molecular profile, then therapy. 50 items per page.
| Therapy | Cancer | Type | Level | Direction · significance | Rating (1–5) | Status | Evidence | Source |
|---|---|---|---|---|---|---|---|---|
| FLT3 D835 + FLT3 I836 + FLT3 ITD1 | ||||||||
| Chemotherapy + MidostaurinCombination | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 4 | submitted | EID11261In this phase III randomized, double-blind placebo-controlled trial, 717 patients with FLT3 mutations (tested for ITD or 835 or 836) underwent randomization 1:1 such that 360 were assigned to the mido… (full text at CIViC) PMID 28644114 · Stone et al., 2017 · Open in CIViC | civic |
| FLT3 ITD & TKD MUTATIONS2 | ||||||||
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | submitted | EID8516A Phase III Randomized, Double-Blind study of chemotherapy + Midostaurin or Placebo in newly diagnosed patients < 60 Years of age with FLT3 mutated Acute Myeloid Leukemia (AML). Overall survival was s… (full text at CIViC) PMID 28644114 · Stone et al., 2017 · Open in CIViC | civic |
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8914Murine pro-B lymphocyte lines Ba/F3 cells with FLT3-ITD were exposed to sorafenib with increasing low doses (i.e., 1-5 nmol/L) of sorafenib for up to 3 months, and further exposed for an additional 3 … (full text at CIViC) PMID 24619500 · Zhang et al., 2014 · Open in CIViC | civic |
| FLT3 ITD & Y597F1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 3 | submitted | EID9142Acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITD) mutation is an aggressive hematologic malignancy with a grave prognosis. Targeted deep sequencing was performed on FLT3… (full text at CIViC) PMID 26438511 · Garg et al., 2015 · Open in CIViC | civic |
| FLT3 ITD & Y842C4 | ||||||||
| FLT3 Inhibitor FF-10101 Succinate | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID9082By assessing cell viability using MTS assay, FF-10101 showed growth inhibitory effects on FLT3-ITD with Y842C mutation expressing 32D cells(Figure 3A). Consistently, FF-10101 potently inhibited FLT3 p… (full text at CIViC) PMID 29187377 · Yamaura et al., 2018 · Open in CIViC | civic |
| Ponatinib + SorafenibSubstitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 4 | submitted | EID8895Proliferation of Ba/F3 cells with FLT3 double mutations was studied for the activity of ponatinib and sorafenib. Compared to control cells with native FLT3-ITD mutant (IC50: 3.0nM), cells with double … (full text at CIViC) PMID 23430109 · Smith et al., 2013 · Open in CIViC | civic |
| FLT3 K663Q1 | ||||||||
| Sunitinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | submitted | EID8670From 109 unselected AML patients, one was identified to harbor a FLT3 K663Q mutation in the TK1 domain [outside the juxtamembrane (JM) domain and the activation loop (AL)], homologous to the KIT K642E… (full text at CIViC) PMID 16990784 · Schittenhelm et al., 2006 · Open in CIViC | civic |
| FLT3 M664I1 | ||||||||
| Pexidartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 3 | submitted | EID8667Mutations were identified by in vitro saturation mutagenesis on the background of FLT3-ITD or FLT3-ITD/F691L. Proliferation and biochemical studies showed that the FLT3-ITD M664I (IC50 =0.61μM) and FL… (full text at CIViC) PMID 25847190 · Smith et al., 2015 · Open in CIViC | civic |
| FLT3 M737I1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Does Not Support Oncogenicity | 3 | accepted | EID12961FLT3 M737I variant was found in patient at diagnosis but absent in the remission sample. BaF3 cells was transformed to express M737I and these cells were unable to grow in the absence of IL-3 similar … (full text at CIViC) PMID 18068628 · Fröhling et al., 2007 · Open in CIViC | civic |
| FLT3 Mutation7 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | submitted | EID8266In this cohort, 431 patients (537 specimens underwent targeted NGS, 68 patients underwent more than one sequencing reaction) with an AML diagnosis (new and r/r) were analyzed to identify and character… (full text at CIViC) PMID 30181385 · Schwartz et al., 2019 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 2 | accepted | EID156FLT3 mutations did not alter overall survival or remission duration in younger (16-60), cytogenetically normal AML patients with CEBPA mutations. 10/36 patients with CEBPA mutations also had FLT3 muta… (full text at CIViC) PMID 14726504 · Fröhling et al., 2004 · Open in CIViC | civic |
| Unspecified therapy | Acute Myeloid LeukemiaCURATED_BROADER | |||||||
| FLT3 N676K1 | ||||||||
| Midostaurin + QuizartinibSequential | Core Binding Factor Acute Myeloid Leukemia | Predictive | B | Supports N/A | 3 | submitted | EID8263In a cohort of 84 de novo AML patients with a CBFB/MYH11 rearrangement and in 36 patients with a RUNX1/RUNX1T1 rearrangement, the FLT3 N676K mutation was identified in 5 and 1 patients, respectively (… (full text at CIViC) PMID 23878140 · Opatz et al., 2013 · Open in CIViC | civic |
| FLT3 N841I9 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 1 | submitted | EID9235This study identified genetic driver mutations by sequencing 111 genes and cytogenetic studies in 1540 samples across three different clinical trials. Table S5 shows all mutations identified in the sa… (full text at CIViC) PMID 27276561 · Papaemmanuil et al., 2016 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID12507In 65 hematologic cancer patient samples (53 AML, 9 ALL, and 3 MDS) partially enriched for lacking FLT3 ITD mutations, resequencing of 21/24 FLT3 exons was performed. In 2 patients with AML, the novel… (full text at CIViC) PMID 15178581 · Jiang et al., 2004 · Open in CIViC | civic |
| 〃 | Acute Myeloid Leukemia with NPM1 MutationALIAS | |||||||
| FLT3 N841K2 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 4 | submitted | EID9236This study identified genetic driver mutations by sequencing 111 genes and cytogenetic studies in 1540 samples across three different clinical trials. The prognostic significance of FLT3 tyrosine kina… (full text at CIViC) PMID 27276561 · Papaemmanuil et al., 2016 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 2 | submitted | EID8899The study screened for mutations in the second tyrosine kinase domain of FLT3 (TK2) in 172 untreated patient with de novo AML. Nonisotopic RNase cleavage assay was used to identify samples that did no… (full text at CIViC) PMID 15625552 · Matsuno et al., 2005 · Open in CIViC | civic |
| FLT3 N841T1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | B | Supports Oncogenicity | 4 | submitted | EID9237This study identified genetic driver mutations by sequencing 111 genes and cytogenetic studies in 1540 samples across three different clinical trials. The prognostic significance of FLT3 tyrosine kina… (full text at CIViC) PMID 27276561 · Papaemmanuil et al., 2016 · Open in CIViC | civic |
| FLT3LG Expression + FLT3 OverexpressionFLT3LGFLT32 | ||||||||
| AG1295 + Crenolanib + R406Substitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Does Not Support Sensitivity Response | 3 | accepted | EID11089In some cancers such as infant ALL, B-lineage ALL and AML samples with the highest levels of wild-type FLT3, constitutive FLT3 phosphorylation is seen from paracrine or autocrine activation from FLT3 … (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC | civic |
| FLT3 Tyrosine Kinase Inhibitor TTT-3002 + KW2449 + Lestaurtinib + Linifanib + Midostaurin + Ponatinib + Quizartinib + SunitinibSubstitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | ||||
| FLT3 Q575del3 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 5 | submitted | EID930246-year-old woman with normal karyotype AML; negative for ITD mutation by PCR-based FLT3 testing. Based on negative FLT3-ITD: Treated with phase 1B standard cytarabine and daunorubicin (7+3) induction… (full text at CIViC) PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | 5 | submitted | EID930346-year-old woman with normal karyotype AML; negative for ITD mutation by PCR-based FLT3 testing. Based on negative FLT3-ITD: Treated with phase 1B standard cytarabine and daunorubicin (7+3) induction… (full text at CIViC) PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| Lestaurtinib + Midostaurin + Sorafenib + | ||||||||
| FLT3 S574del1 | ||||||||
| Crenolanib + Lestaurtinib + Midostaurin + Ponatinib + Quizartinib + SorafenibSubstitutes | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID9308The construct supported IL-3 independent growth of Ba/F3 cells. It showed FLT-3 autophosphorylation and downstream signaling via STAT5, AKT, and ERK1/2 pathways. With IL-3 deprivation, the cells showe… (full text at CIViC) PMID 33914060 · Young et al., 2021 · Open in CIViC | civic |
| FLT3 TKD MUTATION7 | ||||||||
| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 4 | accepted | EID373In AML patients, FLT3-TKD mutation was associated with poorer disease free survival compared to patients with wild type FLT3. PMID 17940205 · Whitman et al., 2008 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Better Outcome | 3 | accepted | EID171Event-free survival was significantly improved in patients with both NPM1 and FLT3-TKD mutations compared to patients with 1) FLT3-TKD mutations alone 2) either NPM1 or FLT3-TKD when FLT3-ITD patients… (full text at CIViC) PMID 17965322 · Bacher et al., 2008 · Open in CIViC | civic |
| (diagnostic) | Acute Myeloid LeukemiaCURATED_BROADER | Diagnostic | ||||||
| FLT3 V592_D593INSDFREY4 | ||||||||
| Palbociclib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID4742In an in vitro study, MOLM-14, PL21 and MV4-11 cell lines expressing FLT3 internal tandem duplication mutation (FLT3-ITD) demonstrated increased sensitivity to palbociclib treatment, compared to THP-1… (full text at CIViC) PMID 27099147 · Uras et al., 2016 · Open in CIViC | civic |
| Sunitinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | C | Supports Sensitivity Response | — | submitted | EID4739In a retrospective study of 15 acute myeloid leukemia patients, the patients with FLT3 internal tandem duplication mutation (n=2) were associated with improved response to sunitinib treatment. The pat… (full text at CIViC) PMID 15459012 · Fiedler et al., 2005 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | |||||||
| FLT3 V592G1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID13031The FLT3 V592G variant was found in a patient with AML. BaF3 cells transformed to express V592G demonstrated proliferation in the absence of IL-3 similar to D835Y positive control. Cell proliferation … (full text at CIViC) PMID 18068628 · Fröhling et al., 2007 · Open in CIViC | civic |
| FLT3 V592I1 | ||||||||
| (oncogenic) | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 2 | rejected | EID12964Longitudinal study analyzing blood samples over time for CHIP. The V592I was found with a VAF 0.53% (below normal CHIP threshold) in a control individual who did not develop AML. PMID 31004019 · Young et al., 2019 · Open in CIViC | civic |
Data updated 21 hours agoSource updated unknownsource: civic (CC0)
Evidence levels, directions and ratings are those assigned by CIViC curators. "Submitted" items have not completed curation review. This is not treatment guidance.
| Acute Myeloid LeukemiaCURATED_BROADER |
| Predictive |
| D |
| Supports Resistance |
| 4 |
| submitted |
EID9081To study pro-apoptotic effects against AML cells harboring FLT3-ITD and/or TKD mutations by selinexor, apoptosis induction was assessed as the percentage of annexin V–positive cells by flow cytometry.… (full text at CIViC) PMID 29773601 · Zhang et al., 2018 · Open in CIViC |
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| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Resistance | 4 | submitted | EID8913Murine pro-B lymphocyte lines Ba/F3 cells with FLT3-ITD were exposed to sorafenib with increasing low doses (i.e., 1-5 nmol/L) of sorafenib for up to 3 months, and further exposed for an additional 3 … (full text at CIViC) PMID 24619500 · Zhang et al., 2014 · Open in CIViC | civic |
| Predictive |
| C |
| Supports N/A |
| 2 |
| submitted |
EID8888In this retrospective analysis of 7 diagnostic specimens from patients with AML-Normal Karyotype (AML-NK), which also included 2 remission specimens and 1 relapse specimen (n =10), described a targete… (full text at CIViC) PMID 23702683 · Conte et al., 2013 · Open in CIViC |
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| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 4 | accepted | EID7283In a phase 1/2 trial, patients with refractory or relapsed AML with FLT3 mutation (n=191; ITD n=162, D835 n=13, ITD-D835 n=16) received gilteritinib. 49% (93/191) of patients achieved an overall respo… (full text at CIViC) PMID 28645776 · Perl et al., 2017 · Open in CIViC | civic |
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | A | Supports Sensitivity Response | 3 | accepted | EID5261Midostaurin is FDA-approved for the treatment of newly-diagnosed acute myeloid leukemia patients harboring FLT3 mutations. PMID 28546144 · Levis, 2017 · Open in CIViC | civic |
| Nilotinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | submitted | EID5575Of the 14 AML patients receiving nilotinib, 80% achieved complete remission or complete remission with incomplete platelet recovery. Genetic testing revealed that 27% of these individuals conferred a … (full text at CIViC) PMID 28720666 · Shen et al., 2017 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 4 | submitted | EID5574Compared to non-treated control cells, MV4-11 cells (FLT3 mutated cell line) that were exposed to nilotinib (30 uM) showed a 58% reduction in colony numbers.Further evidence to support cell death incl… (full text at CIViC) PMID 28720666 · Shen et al., 2017 · Open in CIViC | civic |
| Oncogenic |
| C |
| Supports Oncogenicity |
| 1 |
| submitted |
EID12508To study the mutational spectrum in older AML patients over, 22 cases of NPM1-mutated de novo AML in patients older than 75 were sequenced and 76 mutations (50 different variants) were found across 16… (full text at CIViC) PMID 33711909 · Pettersson et al., 2021 · Open in CIViC |
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| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | C | Supports Oncogenicity | 1 | submitted | EID12509Mutational profiling was performed with targeted NGS of 43 genes to analyze potential factors related to response and outcome in older patients with AML at the time of diagnosis enrolled in the FLUGAZ… (full text at CIViC) PMID 34070172 · Ayala et al., 2021 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Oncogenic | D | Supports Oncogenicity | 3 | submitted | EID12506In 2 patients with AML, the novel N841I point mutation was detected by Sanger and Mass spectrometry genotyping. FLT3 N841I was placed into and expressed in Ba/F3 cells, which lead to IL-3 independent … (full text at CIViC) PMID 15178581 · Jiang et al., 2004 · Open in CIViC | civic |
| Gilteritinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12510Ba/F3 cells were manipulated to express FLT3-ITD or the FLT3 Tyrosine Kinase Domain point mutation N841I. These cells were treated with the FLT3 inhibitor, gilteritinib, for 2 days and subsequently ce… (full text at CIViC) PMID 40196870 · Nakazawa et al., 2025 · Open in CIViC | civic |
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 3 | accepted | EID8858Expression of the N841I variant in murine BaF3 cell line resulted in constitutive autophosphorylation of FLT3 and the amount of autophosphorylated FLT3 was decreased with exposure to the FLT3 inhibito… (full text at CIViC) PMID 15178581 · Jiang et al., 2004 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12512Ba/F3 cells were manipulated to express FLT3-ITD or the FLT3 Tyrosine Kinase Domain point mutation N841I. These cells were treated with the FLT3 inhibitor, midostaurin, for 2 days and subsequently cel… (full text at CIViC) PMID 40196870 · Nakazawa et al., 2025 · Open in CIViC | civic |
| Quizartinib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | 2 | submitted | EID12511Ba/F3 cells were manipulated to express FLT3-ITD or the FLT3 Tyrosine Kinase Domain point mutation N841I. These cells were treated with the FLT3 inhibitor, quizartinib, for 2 days and subsequently cel… (full text at CIViC) PMID 40196870 · Nakazawa et al., 2025 · Open in CIViC | civic |
| 3 |
| submitted |
EID11088In some cancers such as infant ALL, B-lineage ALL and AML samples with the highest levels of wild-type FLT3, constitutive FLT3 phosphorylation is seen from paracrine or autocrine activation from FLT3 … (full text at CIViC) PMID 28077790 · Nguyen et al., 2017 · Open in CIViC |
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| Acute Myeloid LeukemiaCURATED_BROADER |
| Predictive |
| D |
| Supports Sensitivity Response |
| 5 |
| submitted |
EID9304In this functional study: FLT-3/Q575Δ rendered transduced Ba/F3 cells (with this construct) to IL-3–independent growth (similar to FLT3 ITS and D835Y), leading to activation of downstream signaling th… (full text at CIViC) PMID 33914060 · Young et al., 2021 · Open in CIViC |
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| B |
| Does Not Support Positive |
| 3 |
| accepted |
EID214WBC counts were not significantly different in AML patients with FLT3 D835 mutations compared to wild type. PMID 11290608 · Yamamoto et al., 2001 · Open in CIViC |
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| (prognostic) | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Does Not Support N/A | 3 | accepted | EID322AML patients with D835 mutation of FLT3 did not have worse overall survival than patients with wild type FLT3. PMID 11290608 · Yamamoto et al., 2001 · Open in CIViC | civic |
| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Prognostic | B | Supports Poor Outcome | 3 | submitted | EID9246This study compares the genetic drivers identified in a relatively young population of patients with AML across three multicenter clinical trials (AML-HD98A, AML-HD98B, and AMLSG-07-04). FLT3 (both IT… (full text at CIViC) PMID 27276561 · Papaemmanuil et al., 2016 · Open in CIViC | civic |
| Midostaurin | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Sensitivity Response | 3 | accepted | EID1295In a phase 2 clinical study of 95 AML/high-risk MDS patients treated with either 50 or 100 mg midostaurin, 35 harbored FLT3 mutations (26 had FLT3 ITD, 9 had FLT3 D835Y mutations). A higher percentage… (full text at CIViC) PMID 20733134 · Fischer et al., 2010 · Open in CIViC | civic |
| Sorafenib | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | B | Supports Resistance | 4 | accepted | EID248Sorafenib is effective in patients with FLT3 internal tandem repeat mutations, but not in patients with wild type or D835 mutation. PMID 18230792 · Zhang et al., 2008 · Open in CIViC | civic |
| Predictive |
| C |
| Supports Sensitivity Response |
| — |
| submitted |
EID4740In a phase I study of 29 acute myeloid leukemia patients, patients with FLT3 internal tandem duplication (ITD) mutation (n=3) were associated with improved response to sunitinib monotherapy compared … (full text at CIViC) PMID 14654525 · O'Farrell et al., 2003 · Open in CIViC |
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| 〃 | Acute Myeloid LeukemiaCURATED_BROADER | Predictive | D | Supports Sensitivity Response | — | submitted | EID4741In an in vitro study, leukemia M4;11 (endogenous), myeloid 32D (overexpression) and Chinese hamster ovary (transient expression) cell lines expressing FLT3 internal tandem duplication mutation demonst… (full text at CIViC) PMID 12531805 · O'Farrell et al., 2003 · Open in CIViC | civic |