Oncofusion

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Epidemiologymoderate confidence 3 of 5: One strong study, or several smaller consistent ones.Q55-calm-af10

How common PICALM::MLLT10 is, and in which disease - 65% T-ALL, 27% AML, and invisible to karyotype half the time

also called CALM-AF10 incidence

This fusion is rare overall but not rare within T-cell leukaemia, where it turns up in roughly one in eleven unselected cases. Half of the cases cannot be seen down a microscope and need a molecular test, so series that rely on chromosome pictures miss them.

The same thing, for a scientist

Across a 156-patient aggregate, PICALM::MLLT10 distributes **T-ALL 65%, AML 27%, ambiguous-lineage 8%**, with a **median age of 24 years** [E1]. Within unselected T-ALL the fusion is present in **9% (12/131)** - 8% of children and 10% of adults [E2] - and the 2026 review gives the commonly quoted range as **6-7%** [E3]. In paediatric AML it is **under 1%** [E3]. **A detection warning belongs in every incidence figure for this fusion: only about half the positive cases showed t(10;11) by classical cytogenetics** [E2], so karyotype-based series systematically undercount it and any historical incidence estimate is a lower bound.

Go deeper
Numbers with their populations attached
measurevaluepopulationsource
lineage splitT-ALL 65%, AML 27%, ALAL 8%156 PICALM::MLLT10 patients (12 institutional + 144 pooled)1
median age24 yearssame1
frequency in T-ALL9% (12/131)unselected T-ALL, adults and children, France2
frequency in T-ALL6-7%as commonly quoted3
frequency in TCR-gamma-delta T-ALL19%same cohort as 22
frequency in immature delta/gamma T-ALL33%same cohort2
frequency in paediatric AMLunder 1%paediatric AML3
detected by classical karyotypeabout 50% of positivessame cohort as 22

The 65%-T-ALL figure and the 9%-of-T-ALL figure are not the same kind of number and are routinely conflated: the first is the composition of the fusion-positive population, the second is the penetration of the fusion into a disease. Both are needed and neither implies the other.

CORRECTION, 2026-09-21: the TCR-lineage figures in this table split by AGE and this entry did not say so

The 19%-in-TCR-gamma-delta and 33%-in-immature-delta/gamma rows, and the accompanying 0% in TCR-alpha-beta, come from one 2003 cohort and are quoted across this graph as 'CALM-AF10 is specific to the TCRgammadelta lineage'. A later prospective molecular screen in the same national network found the immunophenotype splits sharply by age: among 30 of 431 (7%) adults and 15 of 234 (6%) children with CALM-AF10, adults were predominantly (72%) NEGATIVE for surface CD3/T-cell receptor - with 82% of those carrying an early T-cell precursor phenotype - while children were predominantly (67%) POSITIVE for T-cell receptor.

An ETP-dominant adult population is not a TCR-gamma-delta population. So the lineage-specificity statement is age-conditional, and this graph should not carry 'specific to the TCRgammadelta lineage' as an unqualified property of the fusion. The 6-7% and 9% frequency figures are also not in conflict once the detection method is attached to each: only about half of positives are visible by classical karyotype, so every published frequency is partly a statement about the assay.

Facts and figures
metricprevalence within disease
value9
unitpercent of unselected T-ALL
populationunselected T-cell acute lymphoblastic leukaemia, adults and children
regionFrance (founding cohort); consensus range 6-7% across series
year2003
sourceAsnafi et al., Blood 2003 (PMID 12676784); consensus range from the 2026 FEBS Letters review
detection caveatAbout half of fusion-positive cases are cytogenetically cryptic; RT-PCR, FISH or RNA sequencing is required and karyotype-only ascertainment undercounts by roughly a factor of two.
lineage distribution of fusion positive patients
ambiguous_lineage_pct8.000ambiguous_lineage_pct: 8median_age_years24.0median_age_years: 24aml_pct27.0aml_pct: 27t_all_pct65.0t_all_pct: 65n156.0n: 156
paediatric only split
aml_pct40.0aml_pct: 40t_all_pct56.0t_all_pct: 56n98.0n: 98
lineage distribution of fusion positive patients — the numbers behind the chart
{
  "t_all_pct": 65,
  "aml_pct": 27,
  "ambiguous_lineage_pct": 8,
  "n": 156,
  "median_age_years": 24
}
paediatric only split — the numbers behind the chart
{
  "t_all_pct": 56,
  "aml_pct": 40,
  "n": 98
}
How this could bite us back
  • A fusion that is cytogenetically cryptic half the time will be under-enrolled in any trial that screens by karyotype, which biases every reported response rate in it.
  • Quoting '65% T-ALL' as though it were a frequency in T-ALL inverts the denominator, and the two numbers appear one paragraph apart in most reviews.
Still open
  1. What is the true population incidence? Every number here is a prevalence within a tested series, and the cryptic-cytogenetics problem means none of them is an incidence.
  2. Has RNA-sequencing-based ascertainment raised the observed frequency relative to the karyotype era? The prediction is yes and nobody in this reading states it directly.
  3. Is the adult-versus-paediatric lineage difference real, or an artefact of which patients get sequenced?
Every source behind this entry (3)
  1. E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    Among 156 acute leukaemias with PICALM::MLLT10 (12 institutional plus 144 from the literature), median age was 24 years and the lineage split was T-ALL 65%, AML 27%, acute leukaemia of ambiguous lineage 8%.

    What this evidence cannot show

    Literature pooling: 144 of 156 patients come from published reports, which over-represent unusual presentations and may double-count patients appearing in more than one series. Ascertainment differs across decades and across testing platforms.

    Evidence that argues against this (1)
    • A different 98-patient international paediatric cohort gives T-ALL 56% and AML 40% - a materially different split, because it is children only and the fusion's lineage distribution is age-dependent. Mark C et al. 2024
  2. E2strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    CALM-AF10 was detected in 12 of 131 unselected T-ALLs (9%; 8% of children, 10% of adults), of whom only about half showed t(10;11) by classical cytogenetics; frequency was 19% in TCR-gamma-delta and 33% in immature delta/gamma T-ALL, and 0% in TCR-alpha-beta lineage cases.

    What this evidence cannot show

    Single national cohort. The subgroup frequencies rest on small denominators. The cryptic-cytogenetics point is the most transferable finding and is why RT-PCR or RNA-seq is required for ascertainment.

    Evidence that argues against this (1)
    • PUBLISHED CONFLICTING RESULT from the successor screen in the same national network, and it withdraws the lineage-specificity claim for children. Among 30 of 431 (7%) adults and 15 of 234 (6%) children with CALM-AF10, adults were predominantly (72%) negative for surface CD3/T-cell receptor while CHILDREN were predominantly (67%) POSITIVE for T-cell receptor, and 82% of the TCR-negative adults had an early T-cell precursor phenotype. An ETP-dominant adult population is not a TCRgammadelta population, and a TCR-positive paediatric majority is not one either. 'Specific to the TCRgammadelta lineage' holds for the 2003 cohort as reported and does not generalise across age or across the decade of immunophenotyping that followed. Ben Abdelali R et al. 2013
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.review

    PICALM::MLLT10 is detected in approximately 6-7% of T-ALL and in fewer than 1% of paediatric AML cases.

    PICALM::MLLT10 translocated leukemia. · Cullen JM, et al. · FEBS Lett 2026
    What this evidence cannot show

    REVIEW, quoting primary series. Used here as the field's consensus range rather than as an independent measurement; it differs from the 9% in [E2] because of cohort and method.

    Evidence that argues against this (1)
    • PUBLISHED CONFLICTING NUMBERS, and the disagreement is about ascertainment rather than biology. The review's 6-7% sits below the primary screens it summarises: 12 of 131 (9%) unselected T-ALL in one national cohort, and 7% of 431 adults plus 6% of 234 children in another. Only about half of positive cases show t(10;11) by classical cytogenetics, so every published frequency is a statement about the detection method - RT-PCR, RNA-seq or banding - and not about the disease. A review range quoted without its detection methods will read as a consensus when it is an average over instruments of different sensitivity. Ben Abdelali R et al. 2013
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