PLK1 — nominated as an infant-restricted vulnerability, and one of the most essential genes in the genome
also called PLK · polo-like kinase 1 · STPK13
PLK1 is a kinase every dividing cell needs to finish mitosis. One group reports that infant-type MLL-rearranged leukaemia cells are far more sensitive to blocking it than adult-type ones.
The same thing, for a scientist
PLK1 characterises an infant MLLr expression signature, and in a CRISPR/Cas9 KMT2A-rearranged model built in CD34+ cells from human cord blood (infant-mimicking) versus adult bone marrow, PLK1 mRNA is significantly higher in the cord-blood model, confirmed in infant versus adult patients, with a dose-dependent functional response that tracks it. **DepMap gives the opposite kind of number**: pan-cancer Chronos −2.754 with **99.9% of 1,208 lines depleted**, and a KMT2A-selectivity difference that is small and POSITIVE (+0.262 myeloid, +0.134 lymphoid). Both can be true — a differential therapeutic window is not the same as a selective dependency — and the window is the whole question.
Why this entry exists
Found by ana-literature-recall, which measured that this project reads 9.8% of the recent field and named the groups it reads once. Schneidawind C came back with 13 leukaemia papers since 2020 and one citation in the graph. PLK1 had no entry anywhere in 792.
The two numbers, and why they do not cancel
| readout | value |
|---|---|
| PLK1 mRNA, cord-blood vs bone-marrow CRISPR model | significantly higher in cord blood; reproduced in infant vs adult patients |
| volasertib response | dose-dependent fall in proliferation and cell-cycle arrest, most pronounced in the infant model |
| DepMap pan-cancer mean | −2.754 |
| DepMap lines depleted below −0.5 | 99.9% |
| KMT2A-selectivity, myeloid / lymphoid | +0.262 / +0.134 |
A gene that almost every line needs cannot show selectivity on a dependency screen even if a real therapeutic window exists, and a therapeutic window is what the volasertib data describe: more sensitive, not uniquely dependent. The honest reading is that the screen is the wrong instrument for the claim and also the right instrument for the toxicity question, which it answers unfavourably.
depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": -2.6819,
"chronos_mean_other_leukaemia": -2.8913,
"difference": 0.2094,
"pan_essentiality_all_lines": -2.7537,
"selectivity_rank": 17605,
"rank_denominator": 17728,
"provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
"how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}- Does PLK1 expression in KMT2A-rearranged patient samples separate infant from non-infant disease once proliferative index is controlled for?
- Is there any published PLK1 inhibitor trial in paediatric or infant acute leukaemia, as opposed to the adult volasertib experience the paper contrasts with?
- E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
PLK1 characterises an infant MLLr signature; in a CRISPR/Cas9 KMT2A-rearranged model built in CD34+ cells from human cord blood and from adult bone marrow, PLK1 mRNA was significantly higher in the cord-blood model, a difference reproduced by analysing infant versus adult MLLr patients, and expression correlated with a functional response: volasertib produced a dose-dependent decrease in proliferation and cell-cycle arrest, most pronounced in the infant model.
Only Infant MLL-Rearranged Leukemia Is Susceptible to an Inhibition of Polo-like Kinase 1 (PLK-1) by Volasertib · International Journal of Molecular Sciences 2024What this evidence cannot show
Abstract read; full text not read. Cord blood is neonatal and is being used as an infant proxy; this graph separately records that infant KMT2A::AFF1 originates in a FETAL progenitor, so the model's 'infant' arm is one developmental step late.
Evidence that argues against this (2)
- Pan-essentiality is the finding and it argues against the target rather than for it. This gene is depleted in more than 94% of all DepMap lines, which leaves almost no dynamic range in which selectivity could appear, so the small index-versus-comparator difference is uninterpretable rather than small. PLK1 sits at −2.754 with 99.9% of lines depleted, and its KMT2A-selectivity difference is positive in both lineage halves — very slightly LESS required in the index arm. Oncofusion knowledge graph (internal analysis) 2026
- The comparison is between two culture models, not between two patients. Cord blood and adult bone marrow differ in proliferative rate, cytokine dependence and baseline mitotic index, and PLK1 expression tracks proliferation in every tissue. A mitotic kinase being higher in the faster-cycling model is the null hypothesis, not the finding. Cancers 2020
- E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.analysis
In DepMap, PLK1 has a pan-cancer Chronos mean of −2.754 with 99.9% of 1,208 lines depleted below −0.5. Line-normalised and lineage-split against 43 other leukaemia lines, the KMT2A-rearranged index arm gives +0.262 (7 myeloid) and +0.134 (4 lymphoid) — marginally less depleted, not more.
Age-restricted vulnerability panel: PLK1, AURKA, MAT2A and FFAR2 dependency in KMT2A-rearranged leukaemia lines · Oncofusion knowledge graph (internal analysis) 2026What this evidence cannot show
Eleven index lines, four of them lymphoid. No significance test is applied and none would be meaningful at this floor.
Evidence that argues against this (2)
- DepMap contains no infant-derived lines and no age axis, so it cannot test an age-restricted claim. A flat result there does not refute one; it records that the therapeutic case rests on one laboratory's model system with no independent cell-line support. Every line in DepMap is an established adult-derived or paediatric-derived immortalised culture; none is infant-derived and none carries an age annotation usable for this. International Journal of Molecular Sciences 2024
- A positive difference at 99.9% depletion is not evidence of anything. The measurement is at the assay's floor, where Chronos values compress and differences between arms reflect screen noise more than biology. Oncofusion knowledge graph (internal analysis) 2026