Test Directory

• MYB, 6q22.1 Deletion
• IGH::CCND1, t(11;14)
• TP53, 17p13/ATM, 11q22.3 Deletion
• 12cen/13q14.2-q14.3 Deletion

MYB, 6q22.1 Deletion

The deletions of the long arm of chromosome 6 are nonrandom cytogenetic anomalies found in 3% to 7% of cases with chronic lymphocytic leukemia (CLL). Cases of CLL with deletion of 6q have been shown to require a more demanding treatment regimen (Tsimberidou AM et al., 2007). It has been suggested that CLL with 6q- comprise an intermediate-risk group and is predictive of shorter survival (Tsimberidou AM et al., 2007, Cuneo et al., 2004 ). FISH for abnormalities of chromosome 6 can be performed on interphase or metaphase cells.

CCND1:: IGH, t(11;14)

This translocation has earlier been thought to be the hallmark of the mantle cell lymphoma; actually, the frequency of t(11;14) is: 50-70% in mantle cell lymphoma, 10-20% in B-prolymphocytic leukemia, in plasma cell leukemia, and in splenic lymphoma with villous lymphocytes, and 2%-5% in chronic lymphocytic leukemia and in multiple myeloma. This translocation juxtaposes cell-cycle regulator cyclin D1 (CCND1) to immunoglobulin heavy chain (IGH) on chromosome 14q32. Occasionally, immunoglobulin kappa locus (IGK) or immunoglobulin lambda locus (IGL) serve as the CCND1 translocation partner. Secondary genomic alterations are present in >90% of cases and play important roles in pathogenesis. These secondary copy-number changes include gains or amplifications of 3q, 7p, 8q (MYC), 15q, 18q (BCL2), and losses of 1p, 2q, 6q, 8p, 9p (CDKN2A or CDKB2B, in 10–36% of cases), 9q, 10p, 11q (ATM, in 11–57%), 13q (RB1, 25–55%), 17p (TP53, in 21–45%), and 19p. FISH for abnormalities of chromosome 11;14 can be performed on interphase or metaphase cells.

TP53, 17p13/ATM, 11q22.3 Deletion

In chronic lymphocytic leukemia (CLL), the most frequent chromosomal aberrations are deletions of 13q , 11q, 17p, and trisomy 12. Occurring in 50%-60% of patients, del(13q) removes the DLEU2-mir-15-16 cluster, which regulates expression of anti-apoptotic and cell cycle regulatory proteins. Del(11q), detected in 10-20% patients, removes ATM, and del(17p) detected in 5-10% of patients results in loss of TP53. Trisomy 12 occurs in 15-20% of patients, although the genes involved remain unknown. The most frequently mutated genes in CLL/small lymphocytic leukemia (SLL) at the time of first treatment are NOTCH1 (10-15%), ATM (10-15%), SF3B1 (10%), TP53 (5-10%), and BIRC3 (5%). FISH for abnormalities of chromosome ATM/TP53 can be performed on interphase or metaphase cells.

12cen/13q14.2-q14.3 Deletion

In chronic lymphocytic leukemia (CLL), the most frequent chromosomal aberrations are deletions of 13q , 11q, 17p, and trisomy 12. Occurring in 50%-60% of patients, del(13q) removes the DLEU2-mir-15-16 cluster, which regulates expression of anti-apoptotic and cell cycle regulatory proteins. Del(11q), detected in 10-20% patients, removes ATM, and del(17p) detected in 5-10% of patients results in loss of TP53. Trisomy 12 occurs in 15-20% of patients, although the genes involved remain unknown. The most frequently mutated genes in CLL/small lymphocytic leukemia (SLL) at the time of first treatment are NOTCH1 (10-15%), ATM (10-15%), SF3B1 (10%), TP53 (5-10%), and BIRC3 (5%). FISH for abnormalities of chromosome ATM/TP53 can be performed on interphase or metaphase cells.

I

Specimen Types: Leukemic Blood or Bone Marrow

Preferred Collection Container: Green Top (Sodium Heparin)

Alternate Collection Container: Lavendar Top (EDTA)

Desired Specimen Volume: 3 - 5 mL

Minimum Acceptable Volume: 1 mL

• Lithium heparin is not acceptable.
• Specimens must be collected in a sterile collection container.

Each specimen must be accompanied by a requisition form, script, electronic order or physician note. Each order must indicate the reason for testing (diagnosis).

• Transport to the laboratory at room temperature.
• Store specimen as whole blood, in original tube, at room temperature and deliver to lab within 24 hours.
• If specimen cannot be delivered within 24 hours, store in refrigerator. Do not freeze specimen.
• Specimens collected on the weekends must be refrigerated upon arrival at HNL Lab Medicine.

• Specimen frozen
• Specimen arriving without any form of patient identification (unlabeled)
• Specimen with attached needles
• Specimen arriving with broken or leaking collection tube
• Unfixed specimen treated with fixative

MYB, 6q22.1 Deletion Probe

In a normal cell, the expected signal pattern is two red signals and two green signals. In an abnormal cell containing the deletion, the expected signal pattern is one red signal, and two green signals.

CCND1::IGH, t(11;14) Translocation Probe

In a normal cell, the expected signal pattern is two red signals and two green signals. In an abnormal cell containing a typical translocation, the expected signal pattern is one red signal, one green signal, and two fused signals.

TP53, 17p13/ATM,11q22.3 Deletion Probe

In a normal cell, the expected signal pattern is two red signals and two green signals. In an abnormal cell containing the deletion, the expected signal pattern is one red signal and two green signals for the TP53 deletion and two red signals and one green signal for the ATM deletion.

12cen/13q14.2-q14.3 Deletion Probe

In a normal cell, the expected signal pattern is two red signals, two green signals, and two aqua signals. In an abnormal cell containing a 13q deletion the expected signal patterns are one red signal, two green signals, and two aqua signals or zero red signals, 2 green signals, and two aqua signals. In an abnormal cell containing trisomy 12, the expected signal pattern is two red signals, two green signals, and three aqua signals.

• FISH CLL Panel
• CLL