Mantle cell lymphoma

background

Mr.Craig 58 healthy male

Physically active

Chest X ray showed enlarged lymph nodes

Biopsy confirmed Mantle cell lymphoma

a rate and aggressive type of non-hodgkins lymphoma arising from B-cell in the mantle zone of lymph nodes

No symptoms

his age and food health made him an ideal candiate for aggressive induction chemotherapy for complete remission

followed by autologous stem cell transplant

MCL is driven by

characteristic chromosomal translocation that dysregulates the cell cycle causing uncontrolled B-cell proliferation

Treatments for MCL

Proteome inhibitors

Immunotherapy

HDAC inhibitors

Proteome inhibitors

a class of drugs that block the action of proteamones, large proteins in cells

Immunotherapy drug

Rituximab

monoclonal antibody med used to treat cancers by targeting and eliminating positive B cells

HDAC inhibitors are used if

relapse occurs

Genetic testing for MCL

PCR to detect hallmark translocation

Translocation in MCL

Places cyclin D1 under control of the immunoglobulin heavy chain promoter causing

-over expression of cyclin D1

uncontrolled G1- S cell cycle progression

COVID implications for a pt on Rituximab

destroys B-cells

-severe reduction of antibody production

-poor or absent response to COVID vaccines

-higher risk of severe COVID inf

-longer viral shedding and slower recovery

may need monoclonal antibody therapy or antiviral prophylaxis

PCR-Polymerase chain reaction

A lab tech rapidly makes million copies of DNA

PCR can do what

-detect translocation

-monitor residual disease

PCR works by

denaturing DNA

Annealing primers to target sequences

Extending DNA using polymerase

HDAC inhibitor

HDAC inhibitor block the removal of acetyl groups from histones

-OPEN chromatin structures

-reactivate silenced tumor suppressor genes

-apoptosis of cancer cells

-cell cycle arrest

HDAC inhibitor used

when MCL does not respond to first line of therapy

HDAC drugs

modify epigenetic regulation rather than the DNA seq itself

Hallmark-translocation

causes cyclin D1 overexpression

Cancer cells including MCL cells have

elevated ROS

ROS do

rapid proliferation

Mitochondrial dysfunction

DNA Damage accumulation

In MCL

ROS contributes to genomic instability

Makes cells more vulnerable to oxidative stress-inducing treatments

Proteasome inhibitors exploit cancer cells ROS imbalance by

selective cancer cell death