Does CLL begin neonatal?

Does CLL begin neonatal?

Remember is a long way from mouse to man, but an interesting study...


A common feature of B-cell chronic lymphocytic leukemia (CLL) is chromosomal loss of 13q14, containing the miR15a/16-1 locus controlling B-cell proliferation. However, CLL etiology remains unclear.

CLL is an adult leukemia with an incidence that increases with advancing age. A unique feature of CLL is biased B-cell antigen receptor (BCR) usage, autoreactivity with polyreactivity and CD5 expression, all suggest a role for the BCR in driving CLL pathogenesis.

Among human CLLs, BCRs autoreactive with non-muscle myosin IIA (AMyIIA) are recurrent. Here we identify an unmutated AMyIIA BCR in mouse, with distinctive CDR3 segments capable of promoting leukemogenesis. B cells with this AMyIIA BCR are generated by BCR-dependent signaling during B-1 fetal/neonatal development with CD5 induction, but not in adults.

These early-generated AMyIIA B-1 B cells self-renew, increase during aging and can progress to become monoclonal B-cell lymphocytosis, followed by aggressive CLL in aged mice, often with the loss of a chromosomal region containing the miR15a/16-1 locus of varying length, as in human CLL.

Thus, the ability to generate this defined autoreactive BCR by B-1 B cells is a key predisposing step in mice, promoting progression to chronic leukemia.

The paper concludes...

Our mouse AMyIIA BCR CLL data raises the interesting possibility that distinctive fetal/ neonatal B-1 development in humans may also generate a pool of self-reactive B cells that serve as precursors for unmutated BCR CLLs, where specific BCRs selected by this development, on certain genetic backgrounds, pose a high risk for leukemic progression.

Abstract only...

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13 Replies

  • One rather dislikes the thought that one’s parents could be the source of so much trouble..


    One can also read that the age of one’s parents at the time of conception can have a profound effect upon the health of the resultant child. Women have been told for some time that the eggs provided at birth do deteriorate over time, and thus the healthiest offspring are born in the women’s younger years.

    Recently similar research has been applied to men, and the same age effects noted.

    Following on from this thought it would be interesting to do a survey of the members of this forum on the ages of their parents at the time of their birth..

    A subject for Neil to ponder..

    Dick ( The youngest of three with a big spread of ages between us )

  • Not necessarily genetic... I would tend to think mothers smoking ... Player's Please😜

  • Agree, this is hear a lot about birth defects in children of older mothers. I am the youngest of two with a 10 year gap. Mom was 30 when I was born.


  • Mother 32, Father 34. Waiting to see if any CLL patients say there parents are in there early twenties or teens. Interesting.

  • My parents were 30 when I was born. They both smoked. My mother is in remission from diffused large B cell lymphoma.

  • The Ashkenazi Jews of Eastern Europe have been cited as a possible genetic carrier for CLL, and while I am 2nd generation American Eastern European (identified as Russian, but don't know the actual country) on my mother's side plus have an uncle on that side of the family who died with a leukemia, tells me I may have inherited the genes. My parents were in their 20/30s when I was born.

    I am the only sibling in my family to have the diagnosis. I do not know about the cousins of my generation.

    My grandfather did not identify as Jewish, but with all the violence shown to that group of people, many who emigrated did not identify that fact out of much justified fear. My grandmother died before I was born and I was never told any details of that side of the family.

  • Mother 27, Father 25.

  • Interesting! Mom 40 dad 37. I also had a child at 40!

  • Mother 18, Father 24.

  • Both parents under 30. No familial history of blood cancer in any generation that I'm aware of.


  • Both my parents are/were of Eastern Ashkenazi Jewish background, and my mother was 25, my dad 32 when they had me. My father passed at 91 and my mom is now 88. On my dad's side of the family, I have a cousin with lymphoma, about my age ( 61 ), had her spleen removed, and is stable, and one that died in her late 50's ( about 10 years ago ) of CLL. My mother's aunt had some type of blood disease, which she lived with for a long time, and died in her mid seventies many years ago. So yes, there has been an established genetic link of this background by researchers, and here I am, with CLL diagnosed at 60, but seen starting about 3yrs prior. So far my siblings are ok.

  • Both parents 30 when I was born. Grandma on paternal side died in her early 30's, have never heard what of. My mum, me and my daughter are all prone to chest infections. Both mum and I Have under active thyroids. I've been plagued with anaemia for a lot of my adult life and also sinus infections. No blood disorders of which I am aware. However, years ago these things weren't picked up were they?


  • Parents were 23, father's mother German immigrant who refused to talk about Germany in any way shape or form, so zero history. She forbade my mother to name her kids German names. I always wondered what that was all about. My sister in law's parents were both Ashkenazi but kept that a secret until the end of their life, which was a shock to her. I suspect my grandma did the same. My father died in a plane accident at 34 so no idea how his health would have played out. On the one hand I could go digging for info from my cousins, but on the other hand since I am not sharing my diagnosis with anyone that is not going to happen at this juncture. And I will still have CLL no matter what.

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