Continuing saga of CLL

I have a couple of friends who have watched the same soap opera on TV for more than 25 years.  The plot line twists and turns in bizarre ways, some characters get killed off, new ones added - but the show goes on year after year.  In some ways, the CLL saga is a bit like that.   New drugs making their debut are hyped to the skies, some old drugs fall out of favor.  Some of our CLL experts gain rock star status - for a while, until things change and someone else claims the mantle.  Food fights among patient internet forums are always fun to watch from the safety of sidelines.  Once in a while a truly new drug discovery or new concept in our understanding comes along that changes the landscape.  More often than not, we trundle on with not much happening on any given day.  I have been a devoted fan of this soap opera for the past 10 years!

Very often, I come across interesting little nuggets of CLL information that are not quite big enough for a full review article on this website.  In an attempt to capture these tidbits, I thought I would start this on-going thread. New items will be reported under this heading as they come to my attention.  I will get Radha (our webmaster) to find a way of making the “Tidbits” title heading stand out from the other regular articles so that you can easily find it on the homepage.  In an attempt not to bombard you too many emails, I do not plan to send out any heads-up emails whenever I add a new item to this heading. You will just have to visit the website and click on the “Tidbits” icon to see if there is anything new under this heading.  I will have a full listing of all the items under “Tidbits Archives“. As always, your comments are  welcome but you have to be a registered member and log on before you can participate in the member discussions.

Here is the first tidbit, attached below to get you going.  Remember, there will be no more emails alerting you to future tidbits! (Not to worry, we will continue sending out email alerts to our registered members whenever we publish new full length articles on this website).

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Is a higher percentage of cells with 13q deletion more dangerous?

This question has come up in our prior discussions.  The standard CLL FISH panel looks for four types of chromosomal abnormalities: 13q deletion, 12 Trisomy, 11q deletion and the most dangerous 17p deletion.  Of the lot, 13 q deletion is considered the most favorable prognostic indicator.  Does it make a difference if both alleles have 13q deletion?  (Remember, you have a pair of 13 chromosomes, so it is possible to have one or both of these chromosomes with the relevant bit broken off.  Please browse our recent article on Prognostic Indicators to understand this better).

Does it matter if majority of your CLL cells have 13q deletion, as opposed to just a small percentage? And here is a new wrinkle on the subject, does it matter if the bit broken off is a big piece as opposed to a teensy little piece? The abstract below suggests that the answer to both questions is YES.  Higher percentage of CLL cells with 13q deletion is worse prognosis than lower percentage.  Larger chunks of DNA broken off of the 13th chromosomes means more trouble than if the piece broken off is just a small little piece.  Who knew.

All the same, I will keep an eye out to see if any other research group backs-up these findings or refutes them.  It helps to be patient until the dust settles, sometimes the first word out is not always the correct finding.

Genes Chromosomes Cancer. 2011 May 11. doi: 10.1002/gcc.20885. [Epub ahead of print]

13q14 Deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia.

Dal Bo M, Rossi FM, Rossi D, Deambrogi C, Bertoni F, Del Giudice I, Palumbo G, Nanni M, Rinaldi A, Kwee I, Tissino E, Corradini G, Gozzetti A, Cencini E, Ladetto M, Coletta AM, Luciano F, Bulian P, Pozzato G, Laurenti L, Forconi F, Di Raimondo F, Marasca R, Del Poeta G, Gaidano G, Foà R, Guarini A, Gattei V.

Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy.

Deletion at 13q14 is detected by fluorescence in situ hybridization (FISH) in about 50% of chronic lymphocytic leukemia (CLL). Although CLL with 13q deletion as the sole cytogenetic abnormality (del13q-only) usually have good prognosis, more aggressive clinical courses are documented for del13q-only CLL carrying higher percentages of 13q deleted nuclei. Moreover, deletion at 13q of different sizes have been described, whose prognostic significance is still unknown. In a multi-institutional cohort of 342 del13q-only cases and in a consecutive unselected cohort of 265 CLL, we investigated the prognostic significance of 13q deletion, using the 13q FISH probes locus-specific identifier (LSI)-D13S319 and LSI-RB1 that detect the DLEU2/MIR15A/MIR16-1 and RB1 loci, respectively. Results indicated that both percentage of deleted nuclei and presence of larger deletions involving the RB1 locus cooperated to refine the prognosis of del13q-only cases. In particular, CLL carrying <70% of 13q deleted nuclei with deletions not comprising the RB1 locus were characterized by particularly long time-to-treatment. Conversely, CLL with 13q deletion in <70% of nuclei but involving the RB1 locus, or CLL carrying 13q deletion in ≥70% of nuclei, with or without RB1 deletions, collectively experienced shorter time-to-treatment. A revised flowchart for the prognostic FISH assessment of del13q-only CLL, implying the usage of both 13q probes, is proposed. © 2011 Wiley-Liss, Inc.

PMID: 21563234