CCND3 (cyclin D3) — the scan's rank-4 hit, and the only one of the four with a drug class already in children

This is a prediction, not a measurement. No one has seen this protein in this shape. The colours say how much the software trusts itself, and that is worth reading before anything else — the orange stretches are places the model is effectively saying this part has no fixed shape.

• CDK4/6 inhibition hits the cell cycle of every proliferating tissue. In infants the growth plate is the concern this graph has already raised for a different agent (risk-revumenib-growth-plate-closure-juvenile-rat), and a chondrocyte is a CDK4/6-driven proliferating cell. No juvenile-animal or pediatric skeletal data for palbociclib were located in this cycle and none is cited here, so this is an unquantified risk, not a documented one.
• Neutropenia is the dose-limiting toxicity of this class in adults and the one dose-limiting toxicity in the pediatric COG trial was haematologic [E7]. Adding a myelosuppressive agent to re-induction in a disease whose problem is marrow failure is a real cost.
• Increased CCND3 expression is itself associated with palbociclib resistance [E5]. The cells that most need CCND3 may be the ones least served by inhibiting the kinase it activates.
• If CCND3's essential function is kinase-independent [E5], then the DepMap knockout that put CCND3 at rank 4 and the drug that would be given to patients are measuring different things, and the entire chain of reasoning from the scan to the clinic breaks at that link.
• CDK6 is a fusion output, so it is exposed to the same escape route as every other output: a cell that has stopped depending on the fusion, or a lineage-switched clone, need not keep the dependency.

1. What happened to AMLSG 23-14 / Palbo-AL-1 (NCT02310243)? It is the only trial ever run in exactly this population with exactly this drug class, it closed in 2019, and it has posted nothing. One email to the Ulm group is worth more than any further analysis in this entry.
2. Are the CCND3 mutations found in KMT2A-rearranged AML stabilising gain-of-function changes, as the D-cyclin mutations in lymphoma are, or passengers? The paper body was not readable here and the answer changes whether CCND3 is a driver or a bystander.
3. Does the CCND3 dependency survive lineage conditioning? Re-running the scan's comparison with B-lineage matched controls would separate 'KMT2A-rearranged cells need CCND3' from 'B-ALL cells need CCND3', and this project already has the machinery in ana-depmap-lineage-conditioned.
4. Is CCND3's requirement in KMT2A-rearranged cells kinase-dependent? A CDK4/6-binding-deficient CCND3 rescue experiment would say whether a CDK4/6 inhibitor can ever reach this dependency, and would decide whether the drug class is worth pursuing at all.
5. Does a menin inhibitor plus a CDK4/6 inhibitor combine? The mechanistic case is a differentiation agent paired with a proliferative brake, and nothing read here has tested it in a KMT2A-rearranged model.

1. E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset

   In the coordinator's unbiased scan of 4,589 protein-coding genes, CCND3 ranks 4 by KMT2A-rearranged selectivity (difference -0.623; mean DepMap Chronos gene effect -1.527 across 11 Cellosaurus-annotated KMT2A-rearranged leukemia lines versus -0.904 across 43 other leukemia lines) with a pan-essentiality of -0.348 across 1,208 lines, which places it well outside the pan-essential contaminants that occupy eight of the scan's top twenty places.

   DepMap CRISPR (Chronos) gene effect via the Open Targets Platform GraphQL API, scanned across 4,589 HGNC protein-coding genes and split by Cellosaurus KMT2A gene-fusion annotation; analysis in analyses/depmap-kmt2a-selective-scan/ · Broad Institute DepMap; Cellosaurus (SIB); HGNC; Open Targets Platform; analysis run by this project · Databases and derived analysis 2026
   ▸What this evidence cannot show

   This project's own unreviewed computation, not peer reviewed and not independent of ana-depmap-kmt2a-rearranged-specificity (same statistic, same lines). 11 lines, none infant-derived. 24% of the protein-coding genome. The comparison does not condition on lineage, which matters here more than for most hits because the leading counter-hypothesis is that CCND3 dependence is a B-lineage property. Read as the raw results file, not a publication.

   ▸Evidence that argues against this (1)

   • The same scan ranks HOXA9 961 of 4,589, so it cannot see paralogue-buffered dependencies, and eight of its top twenty are ribosomal or core-machinery genes. A rank is a hypothesis, not a result. analysis run by this project 2026
2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   Novel CCND3 mutations were identified in 5 of 56 pediatric MLL(KMT2A)-rearranged AML patients (8.9%) and 2 of 30 adults (3.3%), while 105 pediatric t(8;21) AML samples carried recurrent CCND1 (2.9%) and CCND2 (7.6%) mutations and no CCND3 mutations, indicating a subtype-specific D-type cyclin mutation pattern; treatment of MLL-rearranged AML cell lines with the CDK4/6 inhibitors abemaciclib and palbociclib blocked G1-to-S cell-cycle progression and impaired proliferation.

   Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia · Matsuo H, Yoshida K, Fukumura K, Nakatani K, Noguchi Y, Takasaki S, et al. (Ogawa S, Adachi S, senior authors) · Blood Advances 2:2879-2889 2018
   PMID 30381403DOI
   ▸What this evidence cannot show

   Read as abstract and key-points section only; the body is not retrievable through PMC or Europe PMC and was not read. The mutation frequency rests on 56 pediatric and 30 adult KMT2A-rearranged cases, so 8.9% is 5 patients. Whether the CCND3 mutations are gain-of-function or stabilising, and whether they were functionally characterised, is NOT established by what was read and must not be asserted. The cell lines used for the CDK4/6 inhibitor experiments are not named in the abstract. The prognostic claim in the key points is specific to pediatric MLL-MLLT3-rearranged patients, not to KMT2A-rearranged AML generally. This is AML; the scan's rearranged panel and this project's main interest are mixed lineage.

   ▸Evidence that argues against this (1)

   • A recurrent mutation in 8.9% of cases is a passenger-versus-driver question, not a dependency claim, and a mutation present in 5 of 56 patients cannot explain a dependency seen across 11 cell lines. CCND3 is separately reported to be essential in B-ALL irrespective of driver mutation, which would predict the same DepMap signal with no KMT2A-specific mechanism at all. Ketzer F et al. 2022
3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   CDK6 is a direct target of the MLL fusion protein in infant ALL: CDK6 mRNA is significantly higher in MLL-rearranged than MLL wild-type infant ALL (P<0.001), siRNA knockdown of MLL-AF4 or MLL-ENL fusion mRNA downregulates CDK6, knockdown of CDK6 but not of the highly homologous CDK4 inhibits proliferation of the MLL-AF4-positive line SEM, and MLL-rearranged leukemia cell lines are sensitive in vitro to the CDK4/6 inhibitor PD0332991 with a remarkable G1 arrest.

   MLL fusion-driven activation of CDK6 potentiates proliferation in MLL-rearranged infant ALL · van der Linden MH, Willekes M, van Roon E, Seslija L, Schneider P, Pieters R, Stam RW · Cell Cycle 13:834-844 2014
   PMID 24736461DOI
   ▸What this evidence cannot show

   Read as abstract only. This is the closest published work to the infant population this project cares about, and it is from the Erasmus/Interfant group. But it is about CDK6, the kinase, not about CCND3, the cyclin — the link from one to the other is the biochemistry of the D-cyclin/CDK6 complex, not an experiment in this paper. Cell-line work plus patient expression; no in vivo or clinical readout. PD0332991 is palbociclib.

   ▸Evidence that argues against this (1)

   • An expression difference plus a knockdown in one cell line is a weaker claim than 'direct target'. Nothing in the abstract read here shows fusion occupancy at the CDK6 locus. Placke T et al. 2014
4. E4strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   AML cells driven by MLL-AF9 are exceptionally reliant on CDK6 but not on its functional homologue CDK4; the preferential growth inhibition from CDK6 depletion is mediated through enhanced myeloid differentiation; CDK6 essentiality extends to cells harbouring alternative MLL fusions and to a mouse MLL-AF9 model; CDK6 is transcriptionally activated by mutant MLL; and the context-dependent effects of lowering CDK6 are closely phenocopied by a small-molecule CDK6 inhibitor then in clinical development.

   Requirement for CDK6 in MLL-rearranged acute myeloid leukemia · Placke T, Faber K, Nonami A, Putwain SL, Salih HR, Heidel FH, Kramer A, Root DE, Barbie DA, Krivtsov AV, Armstrong SA, Hahn WC, Huntly BJ, Sykes SM, Milsom MD, Scholl C, Frohling S · Blood 124:13-23 2014
   PMID 24764564DOI
   ▸What this evidence cannot show

   Read as abstract only. AML, not ALL, and an MLL-AF9 (KMT2A::MLLT3) model rather than the KMT2A::AFF1 biology that dominates infant disease. The CDK4-versus-CDK6 discrimination is the most useful part and is consistent across this and the infant-ALL paper. Again: about CDK6, not about CCND3.

   ▸Evidence that argues against this (1)

   • The mechanism given is differentiation, which is the same mechanism claimed for menin inhibition, DOT1L inhibition and LSD1 inhibition in this disease. When every agent's mechanism is 'induces differentiation', the mechanism is doing little discriminating work, and a differentiation phenotype in a cell line does not predict a clinical response. University of Ulm; Pfizer; National Center for Tumor Diseases et al. 2015
5. E5strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   CCND3 is essential for the proliferation and survival of B-ALL independent of the mutational background, its mRNA exceeds that of CCND1 and CCND2, FOXO1 activates its transcription, its anti-apoptotic effect is independent of the kinase activity of the CCND3-CDK4/6 complex, it contributes to CDK8 transcription, and increased CCND3 expression is associated with development of resistance to palbociclib; the authors conclude that downregulating CCND3 might be superior to inhibiting CDK4/6 kinase activity.

   CCND3 is indispensable for the maintenance of B-cell acute lymphoblastic leukemia · Ketzer F, Abdelrasoul H, Vogel M, Marienfeld R, Muschen M, Jumaa H, Wirth T, Ushmorov A · Oncogenesis 11:1 2022
   PMID 35013097DOI
   ▸What this evidence cannot show

   Read as abstract only. This is simultaneously the best support for CCND3 mattering in B-lineage ALL and the strongest argument that the DepMap signal is not KMT2A-specific: 'independent of the mutational background' is exactly the claim that would make a KMT2A-versus-other comparison uninterpretable without lineage conditioning. The kinase-independence claim, if it holds, breaks the inference from a CCND3 CRISPR knockout to a CDK4/6 inhibitor.

   ▸Evidence that argues against this (1)

   • Against 'lineage, not fusion': the subtype-specific mutation pattern is the hardest thing for a pure-lineage explanation to account for. CCND3 mutations occur in KMT2A-rearranged AML — a myeloid disease — while t(8;21) AML from the same study carries CCND1 and CCND2 mutations and no CCND3 mutations. Lineage alone does not predict that. Matsuo H et al. 2018
6. E6established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registry

   A phase Ib/IIa trial of single-agent palbociclib restricted to acute leukemia with MLL rearrangement (AMLSG 23-14 / Palbo-AL-1, NCT02310243) planned 50 adult patients across 24 German sites with CDK6 target inhibition as a secondary endpoint, records a completion date of July 2019, carries registry status 'unknown', and has no results posted.

   Phase Ib/IIa Study of Palbociclib in MLL-rearranged Acute Leukemias AMLSG 23-14/Palbo-AL-1 · University of Ulm; Pfizer; National Center for Tumor Diseases, Heidelberg · ClinicalTrials.gov 2015
   NCT02310243
   ▸What this evidence cannot show

   Registry record read in full via the ClinicalTrials.gov API on 2026-09-18; has_results is false. Absence of posted results is not a published negative result, and no PubMed search run here found a publication reporting this trial. Adults only (age >= 18), single agent, and enrolment against the Simon two-stage design is not reported, so it is not known whether the trial passed its first stage of 21 patients. Treating this as a negative is an inference, and it should be checked with the Ulm group.

   ▸Evidence that argues against this (1)

   • Unreported trials are common for reasons unrelated to efficacy — funding, slow accrual in a rare subtype, investigator turnover. The registry lists 24 sites for a subtype that is roughly 5-10% of adult acute leukemia, so accrual failure is at least as plausible as a negative signal. Raetz EA et al. 2023
7. E7strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   In the Children's Oncology Group AINV18P1 phase 1 trial, palbociclib combined with standard four-drug re-induction chemotherapy in 12 heavily pretreated children and young adults with relapsed/refractory B- and T-lymphoblastic leukemia and lymphoma produced one dose-limiting haematologic toxicity at the starting dose, a recommended phase 2 dose of 50 mg/m2/day for 21 days, grade 3/4 non-haematologic toxicity comparable to the chemotherapy platform alone, and five complete responses (2 of 4 T-ALL, 3 of 7 B-ALL).

   Palbociclib in combination with chemotherapy in pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia and lymphoma: A Children's Oncology Group study (AINV18P1) · Raetz EA, Teachey DT, Minard C, Liu X, Norris RE, Denic KZ, Reid J, Evensen NA, Gore L, Fox E, Loh ML, Weigel BJ, Carroll WL · Pediatric Blood & Cancer 70:e30609 2023
   PMID 37553297DOI
   ▸What this evidence cannot show

   Read as abstract only. n=12, phase 1, no fusion-status selection reported in the abstract, and responses occurred in a combination with four-drug re-induction chemotherapy, so no response can be attributed to palbociclib. No infants. This establishes tolerability and a pediatric dose, nothing about KMT2A-rearranged efficacy.

   ▸Evidence that argues against this (1)

   • Two further pediatric palbociclib ALL trials on the registry did not deliver: NCT03515200 (St. Jude) was terminated after 12 patients and NCT04996160 (Stanford) completed with 2. A class that three separate pediatric groups could not carry past phase 1 has a feasibility problem in this population independent of its biology. St. Jude Children's Research Hospital 2018
8. E_q77_loc1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

   Cyclin D3's entire subcellular record in UniProt P30281 (fetched 2026-09-21) is two locations - 'Nucleus' and 'Cytoplasm' - both at ECO:0000269 and both citing the SAME single reference, PubMed:15358120. There is no note, no isoform-scoped statement and no second experimental source for either compartment.

   UniProtKB P30281 (CCND3_HUMAN) - SUBCELLULAR LOCATION comment block with evidence codes · UniProt Consortium 2026
   ▸What this evidence cannot show

   A measurement of the database, reported as such, read from the comment array with evidence attached on 2026-09-21. The ECO:0000269 code is genuine, so this record would pass any experimental-evidence filter - which is the point: a filter cannot see that both compartments of a 292-residue protein rest on one 2004 short communication about an unrelated interaction.

   ▸Evidence that argues against this (1)

   • An experimentally coded record with a single supporting reference is fragile in a way the code does not express. A better-supported and condition-scoped result exists and is NOT in the record: influenza infection redistributes cyclin D3 from nucleus to cytoplasm and then degrades it, cell-cycle-independently. So the annotated cytoplasmic pool may be a regulated state rather than a constitutive compartment, and the database does not say so. Fan Y et al. 2017
9. E_q77_loc2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

   The single paper UniProt cites for BOTH of cyclin D3's compartments is an interaction study, not a localisation study: Liu et al. 2004 identify ATF5 as a cyclin-D3-specific partner - cyclin D1 and cyclin D2 do not bind it - confirm the interaction by co-IP and in vitro binding, show by CONFOCAL MICROSCOPY that cyclin D3 colocalises with ATF5 in the nuclear region, and show that cyclin D3 potentiates ATF5 transcriptional activity INDEPENDENTLY OF ITS CDK4 PARTNER.

   Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity. · Liu W, Sun M, Jiang J, Shen X, Sun Q, Liu W, Shen H, Gu J · Biochem Biophys Res Commun 2004
   PMID 15358120DOI
   ▸What this evidence cannot show

   Rule 91 FIRES. The evidence code is correct and there is a microscopy panel in the paper, but the paper's subject is an ATF5 interaction and the localisation is a supporting colocalisation control; it is not the founding observation for cyclin D3's compartments and it is not a quantitative partition. It is also a four-page short communication in BBRC rather than a dedicated cell-biology study. No haematopoietic cells. The reason it is worth reading rather than dismissing is the CDK4-independence of the ATF5 effect, which is the same direction as the kinase-independent anti-apoptotic function this entry records at E5 from an entirely different group.

   ▸Evidence that argues against this (1)

   • Two independent CDK-independent functions for cyclin D3 - transcriptional potentiation of ATF5 here, and anti-apoptosis in B-ALL in Ketzer et al. - are not the same claim and should not be merged. They come from different systems, different decades and different assays, and neither has been reproduced. What they jointly warrant is scepticism that a CDK4/6 ATP-site inhibitor reaches the CCND3 dependency this entry's scan found; they do not jointly establish a mechanism. Ketzer F et al. 2022
10. E_q77_loc3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    Influenza A infection triggers REDISTRIBUTION of cyclin D3 from the NUCLEUS to the CYTOPLASM followed by its proteasomal degradation, and the effect is CELL-CYCLE-INDEPENDENT: knocking down Ccnd3 raises virus titres, and a combined Ccnd3/Rb1 knockdown that restores S-phase progression fails to normalise virus production.

    Cell Cycle-independent Role of Cyclin D3 in Host Restriction of Influenza Virus Infection. · Fan Y, Mok CK, Chan MC, Zhang Y, Nal B, Kien F, Bruzzone R, Sanyal S · J Biol Chem 2017
    PMID 28130444DOI
    ▸What this evidence cannot show

    A virology paper in non-haematopoietic human cells, cited here for one thing only: that cyclin D3's nuclear-versus-cytoplasmic partition is REGULATED and coupled to degradation, rather than being a fixed dual annotation. Nothing about influenza is relevant to this graph. The Rb1 double-knockdown is the control that makes the cell-cycle-independence claim interpretable and is why this is recorded at moderate rather than weak. This paper is not in UniProt's record for P30281.

    ▸Evidence that argues against this (1)

    • Generalising a redistribution seen under viral infection to the resting state of a leukaemic blast is unwarranted, and this entry does not do it. An infected cell is under an interferon programme, and CCND3 has independently been identified as an interferon-stimulated restriction factor, so the redistribution may be part of that programme rather than a general property. The transferable point is narrow: the compartment is regulated by degradation, which is what makes a degrader strategy mechanistically plausible. Liu W et al. 2004
11. E_q77_ct1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    In MICE, cyclin D3 is UNIQUELY required for pre-B cell development. A matched analysis of Ccnd1-/-, Ccnd2-/-, Ccnd3-/- and Ccnd2-/-Ccnd3-/- animals isolates the requirement to cyclin D3; Ccnd3 transcription depends on the common gamma-chain, while pre-B-cell-receptor expression and downstream signalling PREVENT proteasome-mediated degradation of cyclin D3; the protein thereby integrates cytokine and pre-BCR signals to expand the pool of pre-B cells that have successfully rearranged the immunoglobulin heavy chain.

    A unique function for cyclin D3 in early B cell development. · Cooper AB, Sawai CM, Sicinska E, Powers SE, Sicinski P, Clark MR, Aifantis I · Nat Immunol 2006
    PMID 16582912DOI
    ▸What this evidence cannot show

    Murine germline knockouts in NORMAL lymphopoiesis - no leukaemia and no fusion anywhere in the study. A developmental requirement is not a maintenance requirement in an established blast, and germline loss allows compensation that acute loss would not. The four-genotype design is the strength and it is still one laboratory's mouse series. Brief rule 73: this is murine normal B lymphopoiesis, not human infant KMT2A::AFF1.

    ▸Evidence that argues against this (1)

    • The human leukaemia result points at a broader requirement, which weakens the fusion-specific reading of this entry's scan hit: CCND3 is reported indispensable for B-ALL INDEPENDENT OF MUTATIONAL BACKGROUND, with CCND3 mRNA exceeding CCND1 and CCND2. If the requirement is a property of B-lineage blasts generally, the scan's 11 KMT2A-rearranged versus 43 mixed leukaemia lines is a lineage comparison wearing a fusion label - the confound this graph already owns an analysis about. Ketzer F et al. 2022
12. E_q77_ct2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    In MICE, cyclin-D3-deficient animals fail to undergo normal expansion of IMMATURE T LYMPHOCYTES and show greatly reduced susceptibility to T-cell malignancies triggered by specific oncogenic pathways; in HUMAN cells, knockdown of cyclin D3 inhibits proliferation of acute lymphoblastic leukaemias derived from immature T lymphocytes.

    Requirement for cyclin D3 in lymphocyte development and T cell leukemias. · Sicinska E, Aifantis I, Le Cam L, Swat W, Borowski C, Yu Q, Ferrando AA, Levin SD, Geng Y, von Boehmer H, Sicinski P · Cancer Cell 2003
    PMID 14706337DOI
    ▸What this evidence cannot show

    The murine arm is germline knockout; the human arm is knockdown in T-ALL lines with no fusion-status annotation. T-lineage, not the index disease - included because it establishes that the cyclin D3 requirement is LYMPHOID-broad rather than B-specific, which is the relevant boundary for reading this entry's scan hit. Same laboratory as the pre-B study.

    ▸Evidence that argues against this (1)

    • Two lymphoid compartments requiring the same cyclin is an argument AGAINST fusion specificity, not for it. Between the pre-B result, the immature-T result and the driver-independent B-ALL result, the simplest account of this entry's rank-4 DepMap selectivity is that lymphoid blasts need cyclin D3 and the comparator arm of the scan is lineage-mixed. The scan's own author recorded the 11-line, non-infant limitation; the lineage composition of the 43 comparator lines is the specific thing that has not been checked. Ketzer F et al. 2022

• ← part ofThe G1 state in KMT2A-rearranged leukaemia — where CDK6 does a job that is not about the cell cycle at all

  CCND3 is the D-type cyclin partner mutated specifically in KMT2A-rearranged AML

• ← supportsThe whole protein-coding genome: menin is still first, and a metabolic pathway appears (run)

  CCND3 ranks 5 and CDK6 ranks 13 at genome scale, independently of the literature that motivated that entry

• expressed in →Pre-B cell — the stage KMT2A::AFF1 leukaemia never reaches, and why that boundary is informative

  cyclin D3 is UNIQUELY required for pre-B development among the three D-type cyclins, integrating common-gamma-chain transcription with pre-BCR-dependent protein stabilisation

• expressed in →Early T-cell precursor (ETP) — the thymocyte that has not yet given up being myeloid, and where KMT2A-rearranged T-ALL sits

  Ccnd3-null mice fail to expand immature T lymphocytes and resist T-cell malignancy; knockdown blocks human immature-T-derived ALL

• related to →The G1 state in KMT2A-rearranged leukaemia — where CDK6 does a job that is not about the cell cycle at all

  the G1 state cyclin D3 maintains is a checkpoint state - only heavy-chain-rearranged pre-B cells keep the protein stable

• related to →The soluble-nucleoplasm versus chromatin-bound axis - the one localisation readout that keeps a size dimension, and nobody has run it on a KMT2A fusion

  the unrun experiment: if the CCND3 dependency is kinase-independent, a nuclear-versus-soluble fractionation in a B-ALL cell would say which pool a CDK4/6 inhibitor misses

• ← supports4,589 genes with no prior, and menin comes first (run)

  rank 4 of 4,589; selective and not pan-essential (difference -0.623, pan-essentiality -0.348)

• co-occurs with →KMT2A-rearranged acute myeloid leukaemia in children and infants

  recurrent novel CCND3 mutations in 8.9% of pediatric and 3.3% of adult KMT2A-rearranged AML; absent in t(8;21)

• ← regulatesKMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)

  indirect: the fusion transcriptionally drives CDK6, the kinase cyclin D3 activates; fusion knockdown lowers CDK6 in infant ALL

• related to →Infant acute lymphoblastic leukaemia (ALL diagnosed under 1 year of age)

  CDK6 arm of the axis is documented in MLL-rearranged infant ALL; CCND3 itself is inferred from the D-cyclin/CDK6 biochemistry

• ← inhibitsCDK4/6 inhibition in KMT2A-rearranged leukemia — the class was already tried, and the trial never reported

  the clinical handle on the CCND3 dependency is the CDK4/6 ATP site, not CCND3 itself

• ← related toAMLSG 23-14 / Palbo-AL-1 (NCT02310243) — the only trial ever run in MLL-rearranged acute leukemia with a CDK4/6 inhibitor, and it reported nothing

  the clinical test of the axis the CCND3 scan hit sits on

• ← related toBounded failure: the CDK4/6 cell lines behind two therapeutic entries are unrecoverable although the article is marked free access

  the CDK4/6 cell lines remain unnamed although the article is tagged free access