FLT3 ITD
FLT3-ITD refers to an internal tandem duplication mutation in FLT3 (FMS-like tyrosine kinase 3), a receptor tyrosine kinase that is important in hematopoietic cell signaling, proliferation, and survival.
FLT3-ITD refers to an internal tandem duplication mutation in FLT3 (FMS-like tyrosine kinase 3), a receptor tyrosine kinase that is important in hematopoietic cell signaling, proliferation, and survival. In acute myeloid leukemia (AML), FLT3-ITD is a well-recognized oncogenic alteration associated with constitutive activation of FLT3 signaling and clinically relevant disease biology.
Biologically, FLT3-ITD is significant because it can drive leukemic growth and is therefore a major therapeutic target in AML. It is also used in risk stratification and treatment planning, particularly in the context of other molecular features such as DNMT3A, TP53, and RAS-pathway alterations. Recent work has continued to focus on identifying inhibitors that retain activity against FLT3-ITD and on understanding how FLT3-ITD status influences prognosis and response to combinations such as chemotherapy, hypomethylating agents, venetoclax, and tyrosine kinase inhibitors.
Rebuilt from PubMed 10 Sept 2026 · no new papers today
Where the papers sit
9 papers study flt3 itd directly. The themes below are drawn from those 9. 1 new direction follows.
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FLT3 Inhibitor Resistance : FLT3 inhibitor development is moving toward agents and combinations that overcome secondary mutations and NRAS-associated resistance. Nintedanib, XL999, quizartinib and gilteritinib recur alongside F691L and secondary FLT3-ITD mutations. 5 papers · 55.6%
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Lower-Intensity AML Therapy : Lower-intensity AML treatment centers on venetoclax with hypomethylating agents and on mutation-defined prognosis. ASXL1 mutations recur as markers of treatment outcome and remission durability. 2 papers · 22.2%
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CNS Relapse in AML : FLT3-ITD microclones and central nervous system involvement recur as relapse-risk concerns in AML. Intensive chemotherapy, FLT3-targeted therapy and allogeneic transplantation are linked to monitoring and managing these relapses. 2 papers · 22.2%
FLT3-ITD marks persistent sanctuary-site leukemia that can evade marrow remission and molecular detection
The 68-year-old patient with FLT3-ITD-mutated monocytic AML developed isolated CNS relapse during sustained marrow morphological and molecular remission under FLT3-inhibitor maintenance, and later had CSF flow-cytometric evidence of leukemia despite repeatedly negative FLT3-ITD PCR results 42635869Aug. This places FLT3-ITD outside its usual roles as a systemic prognostic marker, leukemic driver, or therapeutic target: marrow remission and negative molecular testing did not exclude persistent CNS disease, whereas CSF flow cytometry continued to detect it. The result supports site-specific CNS surveillance with flow cytometry rather than relying on marrow status or FLT3-ITD PCR alone.
Recent Findings on FLT3 ITD
The FLT3-targeted therapy studies converge on suppressing FLT3-ITD signaling while addressing acquired resistance in acute myeloid leukemia 42696088Sep42035942Apr41889033Mar. XL999 and nintedanib overcame secondary mutations, including F691L, in cell, primary-sample, and mouse models, whereas S1PR modulators resensitized NRAS-mutated cells for several variants but not G12C 42696088Sep42230959Jun42035942Apr. Compound 35 selectively inhibited FLT3-ITD, suppressed STAT5, Akt, and Erk signaling, induced G2/M cell-cycle arrest, and triggered apoptosis 41889033Mar. Clinical data linked high CD135 expression with poorer OS and PFS, while TKI combined with chemotherapy improved OS in patients with high CD135 expression and FLT3-ITD mutations 42067641May. The evidence differs in maturity rather than direction, moving from preclinical FLT3 inhibitors and resistance-sensitizing combinations toward biomarker-guided clinical testing.
Lower-intensity therapy studies examine whether venetoclax with hypomethylating agents can maintain complete remission while limiting treatment exposure and incorporating genetic risk 42171770May42089434May. In a case series, six of seven patients remained in continuous remission for 7–50 months after stopping HMA-VEN at six months, and five cleared somatic mutations and cytogenetic abnormalities 42171770May. One patient with FLT3-ITD relapsed after 14 months but achieved a second hematologic remission after HMA-VEN resumed 42171770May. The ASXL1 analysis identifies the prognostic significance of ASXL1MUT across contemporary LIT+VEN backbones as controversial, particularly because its favorable-risk classification requires absence of FLT3-ITD, RAS, and TP53 mutations 42089434May. These reports support selected treatment discontinuation while emphasizing genotype-specific risk assessment.
The two reports show that FLT3-ITD-associated relapse can remain clinically or molecularly occult, including during apparent remission 42635869Aug42166362May. A case report identified isolated CNS relapse despite bone marrow remission, complete donor chimerism, and FLT3 inhibitor maintenance, with recurrent disease involving the optic nerve and causing vision loss 42635869Aug. CSF flow cytometry detected leukemic blasts when repeat FLT3-ITD PCR results were negative, demonstrating immunophenotypic-molecular discordance under FLT3-targeted therapy 42635869Aug. A cohort study found that FLT3-ITD microclones independently increased relapse risk, and 41.8% of relapses with diagnostic microclones involved a macroclone at relapse 42166362May. Together, these findings support sensitive NGS-based detection, CSF flow cytometry, and prospective management strategies for hidden or evolving FLT3-ITD disease.
Written from 9 PubMed abstracts, each one cited by PMID above. Published: 2026-06-15. Last written: 2026-09-06 by GPT. Drafted by language models from published abstracts; not medical advice.