Table 2 Common differentially expressed genes in chemoresistant and chemosensitive classes in comparison with normal controls

BAG3

Anti

Down

Down expression of BAG3 increases apoptosis induced via Bax or Fas by IL-3 deprivation in hematopoietic cells. Furthermore, BAG3 down modulation is recently shown to enhance the apoptotic response to chemotherapy with alkylating agents through regulation of CHK2 and CDC2 proteins in human primary B chronic lymphocytic leukemia cells.

BCL10

Pro

Up

This gene contains a CARD domain, and has been shown to induce apoptosis and to activate NF-kappaB. It is interesting that deregulation of this gene leads to pathogenesis of hematopoietic malignancy. We detected it in HSC from our cohort of patients. Its over expression in CR CD34+ cells could be related to their proneness to death induction.

BCL2L10

Pro

Down

The protein of this gene act as pro-apoptotic regulators that are involved in a wide variety of cellular activities, interacting with other members of BCL-2 protein family including BCL2, BCL2L1/BCL-X(L), and BAX.

BCLAF1

Pro

Up

This gene encodes a transcriptional repressor that interacts with several members of the BCL2 family. Its overexpression induces apoptosis.

BIRC4

Anti

Down

It is a protein which inhibits apoptosis through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2. It also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7.

BIRC8

Anti

Down

BIRC8 is involved in the control of apoptosis by direct inhibition of caspase 9.

BNIP1

Anti

Down

BNIP genes area members of the BCL2/adenovirus E1B 19 kd-interacting protein (BNIP) family. They interact with the E1B 19 kDa protein which is responsible for the protection of virally-induced cell death, as well as, E1B 19 kDa-like sequences of BCL2.

BNIP2

Anti

Down

BNIP3

Pro/Anti

Down

BNIP3 interacts with the E1B 19 kDa protein which is responsible for the protection of virally-induced cell death, as well as E1B 19 kDa-like sequences of BCL2. The dimeric mitochondrial protein is known to induce apoptosis, even in the presence of BCL2.

CARD6

Anti

Down

This protein is a microtubule-associated protein that has been shown to interact with receptor-interacting protein kinases and positively modulate signal transduction pathways converging on activation of the inducible transcription factor NF-kB.

CASP14

Pro

Down

Caspases encode members of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis by inducing of either TNF or FAS-receptor.

CASP5

Pro

Down

CD70

Pro

Down

This cytokine is also reported to play a role in regulating B-cell activation, cytotoxic function of natural killer cells, and immunoglobulin synthesis. Its downexpression could confirm that CD34+ cells from these patients have an expression profile prone to apoptosis and to positively respond to chemotherapy

CFLAR

Anti

Down

c-FLIP inhibits caspase 8 activation and apoptosis mediated by death receptors, such as Fas. Furthermore, overexpression of c-FLIP potently inhibits apoptosis induced by chemotherapy, suggesting that c-FLIP has a role in mediating chemoresistance.

CIDEA

Pro

Down

Cidea that has been shown to activate apoptosis by disrupting a complex consisting of DFF40/CAD.

DAPK1

Pro

Down

This gene commonly results over expressed in hematopoietic malignancies, but it is down regulated in patients after chemotherapy. It could be considered a CR marker.

DFFA

Pro

Up

DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis.

NOL3

Anti

Down

NOL3, an apoptosis suppressor limited to terminally differentiated cells, is induced in human breast cancer and confers chemo-and radiation-resistance.

TNFRSF11B

Anti

Down

Downexpression of this gene in our model could be considered a CR marker: this gene commonly results over expressed in hematopoietic malignancies, but it is down regulated in patients after chemotherapy

TNFRSF9

Anti

Down

This receptor contributes to the clonal expansion, survival, and development of T cells. It can also induce proliferation in peripheral monocytes, enhance T cell apoptosis induced by TCR/CD3 triggered activation.

TNFSF8

Anti

Down

This gene commonly results over expressed in hematopoietic malignancies, but it is down regulated in patients after chemotherapy. It could be considered a CR marker.

TP53BP2

Pro

Down

This protein is localized to the perinuclear region of the cytoplasm, and regulates apoptosis and cell growth through interactions with other regulatory molecules including members of the p53 family.

TP73

Pro

Down

This gene commonly results over expressed in hematopoietic malignancies, but it is down regulated in patients after chemotherapy. It could be considered a CR marker.